DSP
Desmoplakin (DP) (250/210 kDa paraneoplastic pemphigus antigen)
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The loss of central norepinephrine (NE) released by neurons of the locus coeruleus (LC) occurs with aging, and is thought to be an important factor in producing the many of the nonmotor symptoms and exacerbating the degenerative process in animal models of Parkinson's disease (PD). We hypothesize that selectively depleting noradrenergic LC neurons prior to the induction of chronic neuroinflammation may not only accelerate the rate of progressive neurodegeneration throughout the brain, but may exacerbate nonmotor and motor behavioral phenotypes that recapitulate symptoms of PD. For this reason, we used a "two-hit" mouse model whereby brain NE were initially depleted by DSP-4 one week prior to exposing mice to LPS. We found that pretreatment with DSP-4 potentiated LPS-induced sequential neurodegeneration in SNpc, hippocampus, and motor cortex, but not in VTA and caudate/putamen. Mechanistic study revealed that DSP-4 enhanced LPS-induced microglial activation and subsequently elevated neuronal oxidative stress in affected brain regions in a time-dependent pattern. To further characterize the effects of DSP-4 on non-motor and motor symptoms in the LPS model, physiological and behavioral tests were performed at different time points following injection. Consistent with the enhanced neurodegeneration, DSP-4 accelerated the progressive deficits of non-motor symptoms including hyposmia, constipation, anxiety, sociability, exaggerated startle response and impaired learning. Furthermore, notable decreases of motor functions, including decreased rotarod activity, grip strength, and gait disturbance, were observed in treated mice. In summary, our studies provided not only an accelerated "two-hit" PD model that recapitulates the features of sequential neuron loss and the progression of motor/non-motor symptoms of PD, but also revealed the critical role of early LC noradrenergic neuron damage in the pathogenesis of PD-like symptoms.
MeSH Terms
- Adrenergic Neurons
- Aging
- Animals
- Benzylamines
- Brain
- Disease Models, Animal
- Dopaminergic Neurons
- Hippocampus
- Inflammation
- Lipopolysaccharides
- Locus Coeruleus
- Male
- Mice
- Mice, Inbred C57BL
- Microglia
- Motor Activity
- Nerve Degeneration
- Neurodegenerative Diseases
- Norepinephrine
- Oxidative Stress
- Parkinson Disease
Keywords
- Chronic neuroinflammation
- Locus coeruleus
- Motor symptoms
- Nonmotor symptoms
- Norepinephrine
- Parkinson’s diseases
- Progressive neurodegeneration
The process of aging involves biological changes that increases susceptibility for disease. In the aging lung disease IPF, GWAS studies identified genes associated with risk for disease. Recently, several of these genes were also found to be involved in risk for COPD or lung cancer. This review describes GWAS-derived risk genes for IPF that overlap with risk genes for lung cancer or COPD. Risk genes that overlap between aging lung diseases, include FAM13A, DSP and TERT. Most interestingly, disease predisposing alleles for IPF are opposite to those for COPD or lung cancer. Studies show that the alleles are associated with differential gene expression and with physiological traits in the general population. The opposite allelic effect sizes suggest the presence of trade-offs in the aging lung. For TERT, the trade-off involves cellular senescence versus proliferation and repair. For FAM13A and DSP, trade-offs may involve protection from noxious gases or tissue integrity. The overlap in risk genes in aging lung diseases provides evidence that processes associated with FAM13A, DSP and TERT are important for healthy aging. The opposite effect size of the disease risk alleles may represent trade-offs, for which a model involving an apicobasal gene expression gradient is presented.
MeSH Terms
- Aging
- Alleles
- Cell Proliferation
- Cellular Senescence
- Desmoplakins
- GTPase-Activating Proteins
- Genetic Variation
- Humans
- Idiopathic Pulmonary Fibrosis
- Lung Neoplasms
- Phenotype
- Pulmonary Disease, Chronic Obstructive
- Risk Factors
- Telomerase
Previous studies demonstrate that the metabolic syndrome is associated with distal symmetric polyneuropathy (DSP). We aimed to determine the magnitude of this effect and the precise components involved. We determined the symptomatic DSP prevalence in the Health, Aging, and Body Composition (Health ABC) study (prospective cohort study, with subjects aged 70-79 years at baseline), stratified by glycemic status (glucose tolerance test) and the number of additional metabolic syndrome components (updated National Cholesterol Education Program/Adult Treatment Panel III definition). DSP was defined as neuropathic symptoms (questionnaire) plus at least one of three confirmatory tests (heavy monofilament, peroneal conduction velocity, and vibration threshold). Multivariable logistic and linear regression evaluated the association of metabolic syndrome components with DSP in cross-sectional and longitudinal analyses. Of 2,382 participants with neuropathy measures (mean age 73.5 ± 2.9 years, 38.2% black, 51.7% women), 21.0% had diabetes, 29.9% prediabetes, 52.8% metabolic syndrome, and 11.1% DSP. Stratified by glycemic status, DSP prevalence increased as the number of metabolic syndrome components increased (P = 0.03). Diabetes (cross-sectional model, odds ratio [OR] 1.65 [95% CI 1.18-2.31]) and baseline hemoglobin A1C (longitudinal model, OR 1.42 [95% CI 1.15-1.75]) were the only metabolic syndrome measures significantly associated with DSP. Waist circumference and HDL were significantly associated with multiple secondary neuropathy outcomes. Independent of glycemic status, symptomatic DSP is more common in those with additional metabolic syndrome components. However, the issue of which metabolic syndrome components drive this association, in addition to hyperglycemia, remains unclear. Larger waist circumference and low HDL may be associated with DSP, but larger studies with more precise metabolic measures are needed.
MeSH Terms
- Aged
- Aging
- Blood Glucose
- Cross-Sectional Studies
- Female
- Humans
- Hyperglycemia
- Male
- Metabolic Syndrome
- Polyneuropathies
- Prevalence
- Waist Circumference
Toxins produced by harmful algae are associated with detrimental health effects and mass mortalities of marine mammals. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is generally used to confirm the presence of algal toxins in marine mammals. Sample preparation and LC-MS/MS methods for the determination of three diarrhetic shellfish poisoning (DSP) toxins (okadaic acid, OA; dinophysistoxin-1, DTX1; dinophysistoxin-2, DTX2) and pectenotoxin-2 (PTX2) in bottlenose dolphin (Tursiops truncatus) urine and tissue samples were evaluated using spike-and-recovery tests. Sample clean-up with either reversed-phase silica or polymeric solid-phase extraction (SPE) reduced interference of sample matrices and improved toxin recoveries, with polymeric SPE showing higher sample loading capacity. LC separation on Xbridge C18 columns using acetonitrile/water gradient elutions with ammonia as the additive was chosen for its high detectivity and sensitivity in the MS detection of DSP toxins in negative ion mode. The retention times of OA, DTX1, and DTX2, separated as negative ions, increased with LC column temperature while the retention time of PTX2, separated as the neutral molecule, was weakly affected. At the same column temperature, retention times of OA, DTX1, and DTX2 gradually increased as the mobile phases aged while the retention time of PTX2 remained unchanged; higher column temperatures resulted in a greater increase in the retention time of each DSP toxin with mobile phase aging. Average recoveries of the 4 toxins in bottlenose dolphin samples ranged from 80% to 130% with relative standard deviations of less than 15% using the LC mobile phases prepared within one week at a column temperature of 30°C or 40°C. The preferred column temperature was 30°C, as the retention times of DSP toxins were less affected by mobile phase aging at this temperature. The limit of detection of each toxin analyzed in bottlenose dolphin samples was 2.8 ng/g or less in tissue samples and 0.7 ng/ml or less in urine.
MeSH Terms
- Animals
- Bottle-Nosed Dolphin
- Chromatography, Liquid
- Diarrhea
- Furans
- Macrolides
- Marine Toxins
- Okadaic Acid
- Pyrans
- Shellfish Poisoning
- Solid Phase Extraction
- Tandem Mass Spectrometry
Keywords
- Bottlenose dolphins
- Diarrhetic shellfish poisoning toxins
- LC–MS/MS
- Mobile phase aging
- Pectenotoxin
- Solid-phase extraction
While global chromatin conformation studies are emerging, very little is known about the chromatin conformation of human telomeres. Most studies have focused on the role of telomeres as a tumor suppressor mechanism. Here we describe how telomere length regulates gene expression long before telomeres become short enough to produce a DNA damage response (senescence). We directly mapped the interactions adjacent to specific telomere ends using a Hi-C (chromosome capture followed by high-throughput sequencing) technique modified to enrich for specific genomic regions. We demonstrate that chromosome looping brings the telomere close to genes up to 10 Mb away from the telomere when telomeres are long and that the same loci become separated when telomeres are short. Furthermore, expression array analysis reveals that many loci, including noncoding RNAs, may be regulated by telomere length. We report three genes (ISG15 [interferon-stimulated gene 15 kd], DSP [Desmoplakin], and C1S [complement component 1s subcomplement]) located at three different subtelomeric ends (1p, 6p, and 12p) whose expressions are altered with telomere length. Additionally, we confirmed by in situ analysis (3D-FISH [three-dimensional fluorescence in situ hybridization]) that chromosomal looping occurs between the loci of those genes and their respective telomere ends. We term this process TPE-OLD for "telomere position effect over long distances." Our results suggest a potential novel mechanism for how telomere shortening could contribute to aging and disease initiation/progression in human cells long before the induction of a critical DNA damage response.
MeSH Terms
- Cells, Cultured
- Chromatin
- Gene Expression Profiling
- Gene Expression Regulation
- Humans
- Myoblasts
- Telomere
- Telomere Shortening
Keywords
- age-dependent gene expression
- cancer
- chromatin
- chromosome looping
- replicative aging
- senescence
- telomerase
Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a heart muscle disease caused by desmosomal gene mutations, and presents as ventricular tachycardia and sudden cardiac death. Although the mean age at onset or diagnosis of ARVC/D are reported to be around the 30-40s, the age-dependent clinical and genetic differences remain unknown. A total of 35 consecutive Japanese probands (23 male) who were clinically diagnosed with ARVC/D were enrolled in the present study, and genetic analysis of PKP2, DSP, DSG2, and DSC2 was done. The mean age at the first symptom and at diagnosis was 38.6±14.8 years and 40.5±17.7 years, respectively. Probands in whom the onset was cardiopulmonary arrest were significantly younger (22.3±15.3 years) than those with arrhythmia (41.1±13.2 years) or congestive heart failure (45.7±8.5 years). On genetic screening, 19 mutation carriers were identified. Although there was no age dependence for each gene mutation carrier, carriers with PKP2 premature stop codon developed the disease at a significantly younger age than other mutation carriers. The initial clinical manifestations in some young probands were very severe, and PKP2 mutations with a premature stop codon would be associated with disease onset at a younger age.
MeSH Terms
- Adolescent
- Adult
- Age Factors
- Aged
- Aging
- Arrhythmogenic Right Ventricular Dysplasia
- Asian Continental Ancestry Group
- Desmocollins
- Desmoglein 2
- Desmoplakins
- Female
- Humans
- Japan
- Male
- Middle Aged
- Mutation
- Plakophilins
The mouse bioassay (MBA) for diarrhetic shellfish poisoning (DSP) toxins has been widely used in many countries of the world. In the Japanese and EU methods, male mice are designated to be used for MBA. Female mice were described to be less susceptible than male mice. To the best of our knowledge, however, there have been no reports on the details of sex differences in susceptibility to DSP toxins. In this study, we investigated whether, and to what extent, female mice are less sensitive to DSP toxins. A lethal dose of okadaic acid (OA), one of the representative DSP toxins, was injected intraperitoneally into mice. The mice were observed until 24 hours after injection. Both male and female mice of ICR and ddY strains, which are designated in the Japanese official method, were compared. All the mice were four weeks old and weighed 18-20 g. The experiments were repeated twice. The lethality was 70%-100%. Survival analysis showed no sex differences in susceptibility to OA, but ICR female mice showed significant resistance compared with other groups in one out of two trials. These results indicate that sex differences were not clear but, nonetheless, male mice showed more stable results.
MeSH Terms
- Animals
- Biological Assay
- Disease Susceptibility
- Enzyme Inhibitors
- Female
- Food Inspection
- Injections, Intraperitoneal
- Longevity
- Male
- Mice
- Mice, Inbred ICR
- Mice, Neurologic Mutants
- Okadaic Acid
- Sex Factors
- Shellfish Poisoning
- Species Specificity
- Survival Analysis
Aging degrades motivation, cognition, sensory modalities and physical capacities, essentially dimming zestful living. Bradykinesis (declining physical movement) is a highly reliable biomarker of aging and mortality risk. Mice fed a complex dietary supplement (DSP) designed to ameliorate five mechanisms associated with aging showed no loss of total daily locomotion compared with >50% decrement in old untreated mice. This was associated with boosted striatal neuropeptide Y, reversal of age-related declines in mitochondrial complex III activity in brain and amelioration of oxidative stress (brain protein carbonyls). Supplemented mice expressed approximately 50% fewer mitochondrial protein carbonyls per unit of complex III activity. Reduction of free radical production by mitochondria may explain the exceptional longevity of birds and dietary restricted animals and no DSP is known to impact this mechanism. Functional benefits greatly exceeded the modest longevity increases documented for supplemented normal mice. Regardless, for aging humans maintaining zestful health and performance into later years may provide greater social and economic benefits than simply prolonging lifespan. Although identifying the role of specific ingredients and interactions remains outstanding, results provide proof of principle that complex dietary cocktails can powerfully ameliorate biomarkers of aging and modulate mechanisms considered ultimate goals for aging interventions.
MeSH Terms
- Aging
- Animals
- Brain
- Dietary Supplements
- Electron Transport Complex III
- Female
- Growth Hormone
- Humans
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Mitochondria
- Motor Activity
- Neuropeptide Y
- Neurotransmitter Agents
- Oxidative Stress
- Protein Carbonylation
- RNA, Messenger
To investigate the effects of fetal nanoparticle exposure on reproductive function in male mice offspring. Animal study. Academic research laboratory. Forty pregnant ICR mice and 120 male offspring. Two hundred microg of 14-nm carbon nanoparticles was administered intratracheally on days 7 and 14 of gestation, and reproductive function of male offspring was determined at ages 5, 10, and 15 weeks after birth. Maternal and fetal growth, histologic changes in the testes, and daily sperm production (DSP). Histologic examination showed partial vacuolation of seminiferous tubules. and cellular adhesion of seminiferous epithelia was reduced at all three ages. In addition, DSP was significantly decreased in fetal carbon nanoparticle-exposed mice. The DSP in the fetal carbon nanoparticle-exposed mice decreased by 47% at the age of 5 weeks, by 34% at the age of 10 weeks, and by 32% at the age of 15 weeks. On the other hand, nanoparticle administration had no marked effect on body weight, testicle weight, epididymis weight, or serum testosterone concentration. These findings suggest that fetal nanoparticle exposure affects the reproductive function of male offspring. In the future, it would be necessary to clarify the onset mechanisms of nanoparticle-induced male reproductive disorders.
MeSH Terms
- Aging
- Animals
- Carbon
- Female
- Gestational Age
- Male
- Mice
- Mice, Inbred ICR
- Nanoparticles
- Pregnancy
- Prenatal Exposure Delayed Effects
- Reproduction
- Sperm Count
- Sperm Motility
- Spermatogenesis
- Testis
- Testosterone
To study whether Danggui Shaoyao Powder (DSP) is by way of improving pineal function to realize its anti-aging effects. Forty aged rats were randomly divided into the sham operated group (A), the pinealectomized group (B), the sham medicated group (C), the pinealectomized and medicated group (D). The medication given was gastric perfusion of DSP for 3 weeks. Learning and memory ability of rats was observed using Morris water maze and the serum melatonin (MLT) concentration of the rats was measured by radio-immunoassay. The average escape latency in Group B was significantly longer than that in other groups (P <0.05). The times of passing through the platform and the percentage of swimming distance in Group C were significantly higher than those in other groups (P <0.05). The serum MLT was higher at daytime than at night in Group C and D (P <0.05); that at daytime in Group C was higher than Group A (P <0.05) and also higher in Group D than Group B; that at daytime was higher in Group C than Group D; that at night markedly decreased in Group D as compared with Group B (P <0.05). DSP could increase the melatonin secretion and improve learning and memory ability. Since its effects reduced after pinealectomy, it could be deduced that improving pineal function should be one of the action mechanisms for anti-aging.
MeSH Terms
- Aging
- Animals
- Drugs, Chinese Herbal
- Learning
- Melatonin
- Memory
- Pineal Gland
- Powders
- Rats
Primary fixation is never perfectly stable, but is frequently interrupted by slow drifts, microsaccades and saccadic intrusions (SI). SI are involuntary, conjugate movements which take the form of an initial fast movement away from the desired eye position and followed after a short duration, by either a return secondary saccade or a drift. The purpose of this study was to examine the prevalence and metrics of SI in a population of 50 healthy subjects. Using both one and two dimensional recordings we find that all 50 members of the subject group exhibited SI. The SI were bilateral, conjugate and horizontal. No purely vertical SI were detected when examined in three subjects. SI amplitude mean and range was 0.6 degrees /-0.5 degrees, 0.1 degrees -4.1 degrees; SI frequency mean and range was 18.0 /-14.3 per min, 1.0-54.8 per min; SI duration mean and range was 225 /-150, 20-870 ms. The mean SI amplitude and frequency when SI<0.5 degrees were removed was 0.97 degrees /-0.56 degrees and 7.0 /-11.4 per min respectively. Age was positively correlated with SI amplitude (p<0.01), but there was no correlation between age and SI frequency. Three of four types of SI monophasic square wave intrusions (MSWI), biphasic square wave intrusions (BSWI) and double saccadic pulses (DSP) were found to be exclusively saccadic, whilst the fourth type, the single saccadic pulses (SSP), were confirmed to exhibit a slow secondary component. MSWI were the most frequently observed SI occurring in 47 out of 50 (94%) of the subjects with a mean amplitude, frequency and duration of 0.7 degrees /-0.5 degrees, 11.5 /-11.6 per min, and 255 /-147 ms respectively. Mean amplitudes and frequencies for BSWI (n=20), SSP (n=11) and DSP (n=34) were found to be 0.50 degrees /-0.2 degrees, 1.2 /-2.5 per min; 0.40 degrees /-0.20 degrees, 0.4 /-1.0 per min and 0.3 degrees /-0.4 degrees, 5.0 /-8.7 per min respectively. No differences in MSWI characteristics were found between binocular and monocular viewing. Possible explanations for SI occurrence include experimental viewing conditions, subject fatigue and covert shifts in attention.
MeSH Terms
- Adult
- Aged
- Aging
- Fixation, Ocular
- Humans
- Middle Aged
- Reference Values
- Saccades
- Vision, Binocular
- Vision, Monocular
This study sought to determine the effects of ageing on the in vivo micturition characteristics of male Wistar rats and to assess whether they might be replicated in young rats by using the neurotoxin DSP-4 to lesion locus coeruleus-derived noradrenergic pathways projecting to spinal cord nuclei controlling micturition. Significant age-related changes in micturition patterns were observed. There was a loss of a diurnal rhythm in micturition patterns and a large increase in voided volume, maximal between 21 and 24 months, which was paralleled by an increased water intake. DSP-4 lesions neither altered micturition patterns nor water intake in the young adult rat. DSP-4 induced changes in the pattern of tyrosine hydroxylase-like immunoreactivity (TH-LI), most notably almost complete depletion of TH-LI in the dorsolateral nucleus and retention of TH-LI in lumbosacral autonomic preganglionic nuclei, did not mimic the changes in the pattern of TH-LI seen in aged rats.
MeSH Terms
- Aging
- Animals
- Autonomic Fibers, Preganglionic
- Benzylamines
- Central Nervous System
- Circadian Rhythm
- Drinking
- Immunohistochemistry
- Locus Coeruleus
- Male
- Neurotoxins
- Rats
- Rats, Wistar
- Tyrosine 3-Monooxygenase
- Urination
Currently, yessotoxin is regulated among the toxins in the diarrhetic shellfish poisoning (DSP) complex. Yessotoxin is equally acutely toxic towards mice upon intraperitoneal injections as those algal toxins giving diarrhea, but is not diarrheagenic. Its presence in mussels may therefore lead to overestimation of risk of DSP in consumers when the standard mouse bioassay is used. Arguments are presented for the use of analytical methods instead of the mouse bioassay for the diarrheagenic DSP toxins and yessotoxin. Yessotoxin was found to be more than ten times less toxic to mice via the oral route, compared with intraperitoneal injections. Even at 10mg/kg body weight, the highest dose ever tested orally, yessotoxin did not kill the mice. By means of light microscopy of several organs, moderate changes were only observed in the heart. Ultrastructural studies revealed swelling of heart muscle cells leading to separation of the organelles. Effects were most pronounced close to the capillaries. The pathological changes were clearly dose dependent, and the lowest oral dose where any effects were seen was 2.5mg yessotoxin per kg.
MeSH Terms
- Administration, Oral
- Animals
- Dose-Response Relationship, Drug
- Ethers, Cyclic
- Female
- Heart
- Injections, Intraperitoneal
- Longevity
- Mice
- Mitochondria
- Mollusk Venoms
- Muscle Fibers, Skeletal
- Myocardium
- Oxocins
- Shellfish
- Toxicity Tests, Acute
Endocrine and testicular responses to unilateral castration on 1, 10, 56, or 112 days of age were characterized in 132 Chinese Meishan (MS) x White composite (WC) crossbred boars in which testicular size associates with a quantitative trait locus (QTL) on X chromosome. At 220 days of age, testicles of boars unilaterally castrated on Day 1 or 10 weighed more and had greater total daily sperm production (DSP) than one testicle of bilaterally intact boars (P < 0.05); compensation did not double these two responses. Boars with MS alleles at the X chromosome QTL had smaller testicles, darker colored parenchyma, and lower total DSP than boars with WC alleles (P < 0.05). The MS alleles engendered greater (P < 0.05) plasma FSH and LH during puberty than WC alleles. Plasma FSH increased (P < 0.05) within 48 h of unilateral castration on Days 1, 10, and 56. Subsequent increases occurred earlier during puberty (P < 0.05) after unilateral castration at younger ages than after unilateral castration at older ages. Pubertal increases in plasma FSH and LH were greater (P < 0.05) in boars with MS alleles than in those with WC alleles for the X chromosome QTL. Breed of Y chromosome had no effect on testicular traits, FSH, testosterone, or estrone. For LH, boars with an MS Y chromosome had greater (P < 0.01) plasma LH across all ages than boars with a WC Y chromosome. We conclude that a gene or groups of genes that reside on the porcine X chromosome regulate testicular development and pubertal gonadotropin concentrations.
MeSH Terms
- Aging
- Alleles
- Animals
- Animals, Newborn
- Breeding
- Epididymis
- Follicle Stimulating Hormone
- Genotype
- Gonadotropins, Pituitary
- Luteinizing Hormone
- Male
- Orchiectomy
- Organ Size
- Phenotype
- Sexual Maturation
- Species Specificity
- Spermatogenesis
- Swine
- Testis
- X Chromosome
- Y Chromosome
Approximately 2 million women in the USA and Europe continue taking oral contraceptives each year during undetected pregnancy due primarily to non-compliance and also to individual variation in sensitivity to hormones in the contraceptives. Prenatal exposure to oral contraceptives containing 17alpha-ethinyl oestradiol (EE) has generally not been associated with an increased incidence of externally observable malformations at birth. The purpose of this study was to assess effects on reproductive organs in adult male mice that had been exposed during gestation day 0 through 17 (equivalent to gestation week 16 in humans) to clinically relevant (approximately 0.5 microg/kg/day) and lower doses of EE. Doses used in this study ranged from 0.002 to 2 microg/kg/day. By 5 months of age, prostate weight was significantly (P < 0.05) higher than controls in most treatment groups of EE (0.02-2 microg/kg). Prostatic androgen receptor populations were significantly elevated only in the 0.02 microg/kg group, suggesting different mechanisms for the increase in prostate weight at different doses. Daily sperm production (DSP) and DSP per gramme of testis were reduced in all treatment groups during adolescence, but not later in adulthood. These findings are consistent with prior studies showing that prenatal exposure of mice to very low doses of a number of oestrogenic chemicals can alter the adult male reproductive system without causing gross external malformations.
MeSH Terms
- Aging
- Animals
- Body Weight
- Epididymis
- Ethinyl Estradiol
- Female
- Gestational Age
- Male
- Maternal-Fetal Exchange
- Mice
- Organ Size
- Pregnancy
- Prostate
- Receptors, Androgen
- Seminal Vesicles
- Sexual Maturation
- Spermatogenesis
- Testis
Studies of serotonin metabolites in body fluids in attempted suicide patients and of post-mortem brain tissue of suicide victims have demonstrated the involvement of the serotonergic neurotransmission system in the pathogenesis of suicidal behaviour. Recently developed neuroimaging techniques offer the unique possibility of investigating in vivo the functional characteristics of this system. In this study the 5-HT2a receptor population of patients who had recently attempted suicide was studied by means of the highly specific radio-iodinated 5-HT2a receptor antagonist 4-amino-N-[1-[3-(4-fluorophenoxy) propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide or 123I-5-I-R91150. Nine patients who had recently (1-7 days) attempted suicide and 12 age-matched healthy controls received an intravenous injection of 185 MBq 123I-5-I-R91150 and were scanned with high-resolution brain single-photon emission tomography (SPET). Stereotactic realigned images were analysed semi-quantitatively using predefined volumes of interest. Serotonin binding capacity was expressed as the ratio of specific to non-specific activity. The cerebellum was used as a measure of non-specific activity. An age-dependent 5-HT2a binding index was found, in agreement with previous literature. Deliberate self-harm patients had a significantly reduced mean frontal binding index after correction for age (P=0.002) when compared with controls. The reduction was more pronounced among deliberate self-injury patients (DSI) (P<0.001) than among deliberate self-poisoning patients (DSP). Frontal binding index was significantly lower in DSI patients than in DSP suicide attempters (P<0.001). It is concluded that brain SPET of the 5-HT2a serotonin receptor system in attempted suicide patients who are free of drugs influencing the serotonergic system shows in vivo evidence of a decreased frontal binding index of the 5-HT2a receptor, indicating a decrease in the number and/or in the binding affinity of 5-HT2a receptors.
MeSH Terms
- Adolescent
- Adult
- Aging
- Female
- Frontal Lobe
- Humans
- Image Processing, Computer-Assisted
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Piperidines
- Radiopharmaceuticals
- Receptor, Serotonin, 5-HT2A
- Receptors, Serotonin
- Self-Injurious Behavior
- Suicide, Attempted
- Tomography, Emission-Computed, Single-Photon
To investigate the effects of intermittent and continuous exposure of lactating rats to Aroclor 1242 (a PCB congener), testis weight, daily sperm production (DSP) and Sertoli cell number per testis were examined in the adult male offspring. Thyroxine (T4) was also measured because of the well-documented effects of polychlorinated biphenyls (PCBs) on this hormone. In experiment 1.3 groups of lactating female rats received daily subcutaneous injections of low (0.8 mg) or high (1.6 mg) doses of Aroclor 1242 in 0.1 ml corn oil from parturition to weaning of pups at 21 days. In experiment II, 3 groups of lactating rats received 2 subcutaneous injections per week of 0.8 or 1.6 mg Aroclor 1242, as in experiment 1. In both experiments, control rats received vehicle alone. Serum T4 was measured at 21 and 90 days of age, and testis weight, DSP and Sertoli cell numbers were examined at 90 days. In experiment I (continuous exposure), both the low (0.8 mg) and high (1.6 mg) doses suppressed T4 concentrations at 21 days of age. Testis weight was increased by 14.8% (LD) and 16.5% (HD) compared with controls. DSP was increased by 20.4% in the low dose and 25% in the high dose animals compared with controls. The number of Sertoli cells per testis was increased by 32.6 and 39.4% in low and high dose animals, respectively. A similar study in which the lactating females were only dosed twice per week (experiment 11) did not show any differences in these parameters. These results indicate that continuous exposure of lactating female rats to PCBs increases testis weight, sperm production and Sertoli cell numbers in the adult male offspring.
MeSH Terms
- Aging
- Animals
- Aroclors
- Body Weight
- Environmental Pollutants
- Female
- Lactation
- Male
- Organ Size
- Rats
- Rats, Sprague-Dawley
- Reference Values
- Sertoli Cells
- Spermatozoa
- Testis
- Thyroxine
Relationships between blood concentration of FSH and testicular size and daily sperm production were evaluated with data obtained from five studies originally designed to investigate regulation of FSH secretion in Meishan (MS), White composite (WC), and crossbreds of these. A minimum of three blood samples/boar were obtained at greater than 4-d intervals for determination of FSH, and testes were obtained at castration or slaughter. In a random sample of boars, FSH was fivefold greater (P < .01) in MS than in WC boars (n = 22/group). Daily sperm production (DSP)/gram of testis (estimated by counting elongated spermatid nuclei in testicular homogenates) was similar in the groups, but testicular weight (TWT), adjusted for body weight, was less (P < .01) in MS than in WC, yielding lower total daily sperm production (TDSP; P < .05) in MS boars. In four populations (one with MS, one with WC, and two with crossbreds; n = 34 males), boars were selected for extremes in FSH concentrations from larger groups. Across all populations, a threefold greater plasma FSH concentration was associated with a 32% smaller TWT (P < .01). Coincident with increased FSH, TDSP was 33% less (P < .05). In 48 MS x WC boars that were selected for divergence in plasma FSH during pubertal development (4 to 6 mo of age), this divergence was retained at 1 yr (P < .01). Retrospectively, the divergence in FSH was also apparent at 2 and 8 wk of age (P < .05), and the boars with elevated FSH had smaller testicles, lower DSP, and lower TDSP (P < .01). These studies document a negative relationship in mature boars between FSH secretion and testicular size accompanied with decreased TDSP.
MeSH Terms
- Aging
- Animals
- Body Weight
- Follicle Stimulating Hormone
- Male
- Retrospective Studies
- Sexual Maturation
- Spermatozoa
- Swine
- Testis
During brain development, before the apparatus of neurotransmission has been set into place, many neurotransmitters act as growth regulators. In adult brain, their role in neurotransmission comes to the fore but neuronal plasticity and other growth-related processes are their continuing responsibility. This has been clearly demonstrated for catecholamines. Previous as well as recent evidence now indicates that thyroid hormones may participate in the developing and adult brain through similar mechanisms. Immunohistochemical mapping of brain triiodothyronine (antibody specificity established by numerous appropriate tests) demonstrated that the hormone was concentrated in both noradrenergic centers and noradrenergic projection sites. In the centers (locus coeruleus and lateral tegmental system) triiodothyronine staining, like that of tyrosine hydroxylase, was heavily concentrated in cytosol and cell processes. By contrast, in noradrenergic targets, label was most prominent in cell nuclei. Combined biochemical and morphologic data allows a construct of thyroid hormone circuitry to unfold: The locus coeruleus is conveniently located just beneath the ependyma of the 4th ventricle. Thyroxine, entering the brain via the choroid plexus, is preferentially delivered to subependymal brain structures. High concentrations of locus coeruleus norepinephrine promote active conversion of thyroxine to triiodothyronine, leading to the preeminence of the locus coeruleus as a site of triiodothyronine concentration. Results of treatment with the locus coeruleus neurotoxin DSP-4 established that axonal transport accounts for delivery of both triiodothyronine and norepinephrine from locus coeruleus to noradrenergic terminal fields. The apparatus for transduction of thyronergic and noradrenergic signals at both membrane and nuclear sites resides in the postsynaptic target cells. Upon internalization of hormone in post-synaptic target cells, genomic effects of triiodothyronine, norepinephrine, and/or their second messengers are possible and expected. The evidence establishes a direct morphologic connection between central thyronergic and noradrenergic systems, supporting earlier proposals that triiodothyronine or its proximate metabolites may serve as cotransmitters with norepinephrine in the adrenergic nervous system.
MeSH Terms
- Adult
- Aging
- Animals
- Brain
- Humans
- Neurotransmitter Agents
- Norepinephrine
- Thyroid Hormones
Selegiline is a selective and irreversible monoamine B inhibitor with the capacity to increase the level of several antioxidative enzymes in rat brain. It can protect adrenergic neurons against injury induced by neurotoxins such as MPTP, DSP-4 and AF64A in animal studies. In addition, the protective action is not limited to catecholaminergic cells, as selegiline can also minimize the loss of developing motoneurons after axotomy. The aim of this study was to determine whether selegiline can protect peripheral catecholaminergic neurons against the neurotoxic effect of 6-OHDA. This kind of protective effect against 6-OHDA neurotoxicity has not been reported before. Wistar albino male rats aged 4 or 24 months were treated with selegiline or saline solution 1 h before 6-OHDA injection. At 2 weeks after the 6-OHDA injection, the superior cervical ganglia (SCG) and submandibular glands (SMG) were studied using catecholamine histofluorescence and immunohistochemistry for tyrosine hydroxylase (TH). The number of TH-positive cells in the SCG and the length and number of adrenergic nerve fibers in the SMG were quantified. Our findings showed that 6-OHDA caused a reduction of TH immunoreactivity and catecholamine histofluorescence in neuronal somata, as well as a decrease in the number and length of adrenergic nerve fibers in the submandibular gland. Selegiline pretreatment protected SCG neurons and their postganglionic nerve fibers in SMG against these changes in a dose-dependent manner. The mechanism through which selegiline exerts its neuroprotective effect is as yet unknown.
MeSH Terms
- Aging
- Animals
- Immunohistochemistry
- Male
- Microscopy, Fluorescence
- Monoamine Oxidase Inhibitors
- Oxidopamine
- Peripheral Nervous System Diseases
- Rats
- Rats, Wistar
- Selegiline
- Superior Cervical Ganglion
- Tyrosine 3-Monooxygenase
We have surveyed a population size of 6633315 from Diseases Surveillance Points (DSP) system in Gansu province for the last eleven years. The annual birth rate was 18.20% with an annual standard mortality rate 545.80/10(5). The annual standard mortality for male and female were 607.53/10(5) and 483.29/10(5) respectively. The major causes of death were Respiratory system diseases, Cardiovascular diseases, Neoplasms, Injuries, Digestive system diseases, Pediatric diseases, Infectious diseases in sequence. In eleven years, there seemed to be a rising trend in the mortalities of following diseases as: Cerebrovascular diseases, Ischemic heart diseases, Rheumatic fever and heart disease, Lung Cancer, Liver Cancer, Cancer of the Esophagus, Intestinal cancer, Cervical cancer, Injury, Congenital abnomalities, to different degrees. However, an obvious descending trend on the morbidity and mortality of infectious diseases was moticed. The average life expectancy was 71.05 years in DSP, with male 69.57 years, and female 72.72 years. Diseases with higher PYLL were Injuries, Neoplasms, Respiratory system diseases and the like. Data suggested not only the prevention andcontrol of infectious diseases, but also the surveillance of injuries and the prevention and control of chronic diseases should be strengthened.
MeSH Terms
- Adolescent
- Adult
- Aged
- Birth Rate
- Cause of Death
- Cerebrovascular Disorders
- Child
- Child, Preschool
- China
- Female
- Health Status
- Humans
- Infant
- Life Expectancy
- Male
- Middle Aged
- Mortality
- Neoplasms
The aim of this study was to determine the role of testosterone, as reflected in the testicular interstitial fluid, in the completion of the first wave of spermatogenesis and to further elucidate its role in spermiogenesis. At weekly intervals beginning with 26-day-old rats, body and testis weights were obtained, testicular interstitial fluid testosterone (TIF-T) was assayed, daily sperm production (DSP) was determined, and testicular tissue was structurally analyzed by light and electron microscopy. At 40 days postpartum, half the rats were treated with ethane dimethanesulphonate (EDS) to temporarily reduce Leydig cells. The other half served as controls and were treated with the vehicle. The timing of EDS treatment was just prior to the elongation of spermatids. At Day 47 (1 week after EDS treatment), TIF-T, testis weight, DSP, and number of Leydig cells were significantly reduced. At Day 54 (2 weeks after treatment), TIF-T had returned to the normal adult level, Leydig cell repopulation was apparent, and testis weight was normal. The DSP returned to normal by Day 61 (3 weeks after treatment). At 1 and 2 weeks after treatment, Step 8-9 spermatids were partially or completely detached from Sertoli cells. Results indicate that a temporary reduction of testosterone during the peripubertal period leads to a temporary reduction of the DSP approximately 1 week later. It is suggested that reduced testosterone is associated with a mid-spermiogenic lesion interfering with stable attachment of Step 8-9 spermatids to Sertoli cells during Stage VIII-IX of the spermatogenic cycle.
MeSH Terms
- Aging
- Animals
- Epithelial Cells
- Epithelium
- Male
- Microscopy, Electron
- Organ Size
- Rats
- Rats, Sprague-Dawley
- Seminiferous Tubules
- Sertoli Cells
- Sexual Maturation
- Spermatogenesis
- Testis
- Testosterone
The present experiment studied whether a dysfunction of the noradrenergic neurons is related to spatial learning impairment by investigating the levels of noradrenaline in the brain and periphery as well as the acquisition of water maze task in saline-pretreated young rats, in noradrenergic neurotoxin (DSP-4)-pretreated young rats and in saline-pretreated aged rats. Aged rats, which had an increased escape latency onto the hidden platform, revealed a decreased noradrenaline content in the heart, but not in the hippocampus, striatum, or hypothalamus, whereas DSP-4-pretreated rats had decreased noradrenaline content in the brain; the acquisition of water maze task was not impaired. These results suggest that the peripheral noradrenergic system can show age-related changes different from those in the central noradrenergic system, and they failed to provide support for the hypothesis that decreased activity of the central noradrenergic nerves is related to impairment in the acquisition of the water maze task.
MeSH Terms
- Aging
- Animals
- Benzylamines
- Brain
- Learning
- Male
- Myocardium
- Neurotoxins
- Norepinephrine
- Rats
- Rats, Wistar
- Spatial Behavior
Analyses of VHDJH rearrangements isolated from murine peritoneal B-1a cells (CD5 , IgMhi, B220lo), peritoneal B-1b cells (CD5-, IgMhi, B220lo), and conventional splenic B cells provide evidence that a unique repertoire of VH regions is displayed by each of these B-cell subsets. The B-1a subset is characterized by a low N-region diversity, by a high frequency of sequence homologies in the VH-D and D-JH junctions, and by a limited exonuclease nibbling of the terminals of the joining gene segments. Through expansion in ageing mice, B-1a clones with these properties are favoured. B-1b cells are similar to conventional B-2 cells with respect to N-region diversity, but are unique in terms of D gene expression. Thus, while most murine pre-B and B cells preferentially use DSP and DFL gene segments in a given reading frame (RF1), B-1b cells frequently express D genes in another reading frame (RF2). Together, these findings provide structural evidence for a model where B-1a, B-1b and B-2 cells are produced by separate progenitors that are active at different stages of ontogeny.
MeSH Terms
- Aging
- Animals
- B-Lymphocyte Subsets
- Base Sequence
- Cell Differentiation
- Clone Cells
- Flow Cytometry
- Gene Rearrangement, B-Lymphocyte
- Genes, Immunoglobulin
- Genetic Variation
- Immunoglobulin Heavy Chains
- Mice
- Mice, Inbred C57BL
- Molecular Sequence Data
- Peritoneal Cavity
- Reading Frames
- Selection, Genetic
- Spleen
- Stem Cells
(-)Deprenyl (selegiline, jumex, eldepryl, movergan), a close structural relative to phenylethylamine (PEA), is a drug with a unique pharmacological spectrum. It is a highly potent and selective, irreversible inhibitor of B-type monoamine oxidase (MAO), a predominantly glial enzyme in the brain. The activity of this enzyme significantly increases with age. (-)deprenyl, the first selective inhibitor of MAO-B described in literature, has become the universally used research tool for selectively blocking B-type MAO. It is the only selective MAO-B inhibitor in clinical use. (-)Deprenyl interferes with the uptake of catecholamines and indirectly acting sympathomimetics because it is handled by the catecholaminergic neuron in a way similar to the physiological substances transported through the axonal end organ and vesicular membrane. The unique behavior of (-)deprenyl is that, in striking contrast to PEA and its relatives it does not displace the transmitter from storage, ie it is not a releaser. The net result is that (-)deprenyl inhibits the releasing effect of tyramine, and at present, is the only safe MAO inhibitor that can be administered without dietary precautions. Maintenance on (-)deprenyl selectively enhances superoxide dismutase (SOD) and catalase activity in the striatum. This effect is unrelated to its effect on MAO-B and the inhibitory effects of the drug on neurotransmitter uptake. Maintenance on (-)deprenyl facilitates the activity of the catecholaminergic system in the brain, and this effect, too, is unrelated to either its effects on MAO or on neurotransmitter uptake. (-)Deprenyl protects the nigrostriatal dopaminergic neurons against selective neurotoxins (6-hydroxydopamine, MPTP, DSP-4).(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH Terms
- Aging
- Alzheimer Disease
- Animals
- Antiparkinson Agents
- Drug Administration Schedule
- Humans
- Parkinson Disease
- Selegiline
- Substantia Nigra
Germ cell degeneration during spermatocytogenesis and meiosis was investigated to explain the age-related decline in daily sperm production (DSP). Numbers of Types A-dark, A-pale, and B-spermatogonia, potential daily sperm production per g parenchyma (PDSP) based on type B-spermatogonia, early primary spermatocytes, and late primary spermatocytes, and DSP per g based on early spermatids were determined in 15 men aged 20 to 48 yr (mean /- SEM, 33 /- 2 yr) and 15 men aged 52 to 90 yr (65 /- 3 yr). Testes obtained within 15 h of death (largely due to trauma or heart failure) were perfused vascularly with glutaraldehyde. The number of each cell type per g parenchyma was calculated as the product of the percentage of nuclei in the parenchyma times a correction factor for section thickness and nuclear diameter divided by the volume of a single nucleus of that cell type. Paired testicular weight was lower (p less than 0.01) in older men (33 /- 3 g) than in the younger men (49 /- 3 g). Younger and older men had similar numbers of A-dark, A-pale, and B-spermatogonia per g parenchyma. PDSP based on late primary spermatocytes and DSP based on early spermatids were lower (p less than 0.01) in older men than in younger men. In younger men, PDSP was similar (p greater than 0.05) between B-spermatogonia and late primary spermatocytes, whereas DSP measured at the spermatid level was abruptly lower than that estimated from younger cell types. Older men showed reduction in PDSP between early and late primary spermatocytes, with further reduction occurring in DSP at the spermatid level.(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Cell Nucleus
- Humans
- Male
- Meiosis
- Middle Aged
- Sperm Count
- Spermatocytes
- Spermatogenesis
- Spermatogonia
- Spermatozoa
- Testis
Previous studies of adult men have failed to reveal a relationship between numbers of Leydig cells in the testes and rates of sperm production, perhaps because of a functional excess of these cells in younger men. Hence, a possible relationship between Leydig cell numbers and sperm production was sought in 50 older men, aged 50-90 years, in whom the Leydig cell population had been depleted by age-related attrition. When these men were sorted by increasing numbers of Leydig cells per man into two, three, or five groups, no difference could be found between or within these groups when daily sperm production per man (DSP); seminiferous tubular volume, diameter, or length; or seminiferous epithelial volume was examined. Furthermore, no significant correlation could be detected between Leydig cell numbers and DSP in these 50 men. The only relationship between numbers of Leydig cells and spermatogenesis appeared to be a threshold effect, in that men with fewer than 60 million Leydig cells (4 in this study) had drastically reduced DSP. Men with few Leydig cells tended to have larger Leydig cells, and the increased size was due to more cytoplasm instead of nucleoplasm. There were weak but significant positive correlations between total Leydig cell cytoplasm per man and DSP and between average size of a Leydig cell and DSP. These findings suggest that a relationship may exist between sperm production and the amount of cytoplasm containing testosterone-producing organelles in surviving Leydig cells of older men.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Cell Count
- Humans
- Leydig Cells
- Male
- Middle Aged
- Seminiferous Tubules
- Sperm Count
- Spermatogenesis
- Testis
- Testosterone
In the preceding paper it was shown that transient neonatal hypothyroidism induced by treatment of rats from birth to day 25 with the goitrogen 6-propyl-2-thiouracil (PTU) is associated with increases in testis wt and DNA content of up to 80% during adulthood. The testis changes were accompanied by similar, though less marked, increases in the wt and DNA content of epididymis and accessory organs. The purpose of this study was to assess sperm production in these enlarged testes and measure changes in sperm reserves in the epididymis. Testes and epididymides were obtained from control rats or rats given PTU from birth to day 25 (designated "treated") at 90, 135, 160, and 180 days of age. Daily sperm production (DSP), efficiency of sperm production (DSP/g testis), and epididymal sperm reserves were measured in all animals. Compared to controls, DSP of the treated rats was increased by 83%, 86%, 136%, and 132% at 90, 135, 160, and 180 days, respectively. Thus, in the treated rats, DSP, like testis wt, plateaued at day 160. In addition, efficiency of sperm production was increased by 15%-30% at all ages in treated animals. Epididymal sperm reserves were also increased in treated rats at all ages, but the correlation between DSP and epididymal sperm reserves was weak. Sperm motility and concentration in caudal epididymal fluid of adult males treated from birth to day 25 with PTU were normal. These males were fertile and sired litters in which pup wt and pup number were normal. These results indicate that neonatal hypothyroidism in rats is associated not only with increased testis size but also with increased efficiency of sperm production, resulting in increases in DSP of up to 140% in these animals during adulthood. Maximal sperm production is reached at 160 days of age in treated rats (compared to 100 days in controls), coinciding with the attainment of final testicular size. This system represents the first experimental model in which such large increases in sperm production can be produced. The neonatal PTU treatment does not appear to impair fertility or alter sperm characteristics when these animals become adults and may be a useful system with which to study factors which normally regulate sperm production.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Epididymis
- Fertility
- Hypothyroidism
- Male
- Organ Size
- Propylthiouracil
- Rats
- Sperm Count
- Sperm Motility
- Spermatogenesis
- Testis
The present study was performed to determine if chronic administration of a high salt diet induces hypertension similarly in young and adult rats and if treatment with DSP-4 alters the development of the hypertension. Three- (young) and ten- (adult) week-old male Sprague-Dawley rats were fed either a standard rat chow diet (0.71% NaCl), a 4% NaCl diet or an 8% NaCl diet for 12 weeks. Systolic blood pressure, using a standard tail-cuff technique, and body weight were recorded weekly during the dietary treatment period. Direct mean arterial pressure, heart rate, heart weight and kidney weight were determined after 12 weeks. Body weight was slightly reduced in young rats on the 8% NaCl diet. A significant increase in blood pressure as well as heart weight was observed only in young rats on the 8% NaCl diet. An increase in kidney weight was observed in both young and adult rats on the 8% NaCl diet. DSP-4 treatment prevented the development of hypertension as well as cardiac hypertrophy in rats fed the high salt diet but had no effect on rats receiving the normal diet. Body and kidney weights were similar in vehicle- and DSP-4-treated rats on the 8% NaCl diet. These results demonstrate that a critical developmental/maturational period exists during which the young rat is susceptible to the hypertensinogenic effects of a high salt diet. An intact central noradrenergic system appears to be necessary for the expression of this enhanced susceptibility and the subsequent development of hypertension.
MeSH Terms
- Aging
- Animals
- Benzylamines
- Blood Pressure
- Diet
- Hypertension
- Kidney
- Male
- Neurotoxins
- Norepinephrine
- Organ Size
- Rats
- Rats, Inbred Strains
- Sodium Chloride
The present study investigated whether an overactive noradrenergic system is related to the impairment in learning/memory in aged subjects. The effects of partial noradrenaline depletion (using the noradrenergic neurotoxin DSP-4) on the acquisition of a water maze task was investigated in young and aged rats, and hippocampal noradrenaline content was correlated with spatial learning performance in similar rats. DSP-4 treatment impaired markedly the acquisition of the water maze task in aged rats, but improved it slightly in young rats. DSP-4 treatment decreased swimming speed, and this effect tended to be more marked in young rats. In the group of control rats, hippocampal noradrenaline tended to correlate positively with spatial bias in aged rats (the rats with the highest noradrenaline content in the hippocampus tended to have the best spatial learning/memory), but negatively in young rats. These results do not support the hypothesis that spatial learning/memory impairment is due to an overactive noradrenergic system in aged rats. Further studies are needed to clarify the reasons of the marked age-related difference in the effects of DSP-4 on the performance of water maze task in rats.
MeSH Terms
- Aging
- Animals
- Benzylamines
- Brain Chemistry
- Cognition
- Hippocampus
- Learning
- Male
- Norepinephrine
- Orientation
- Psychomotor Performance
- Rats
- Rats, Inbred Strains
- Space Perception
- Sympathomimetics
The present study examines the effects of noradrenergic lesions (either DSP-4 i.p. or 6-hydroxydopamine (6-OHDA) into the dorsal noradrenergic bundle on biochemical (noradrenaline (NA), dopamine (DA), serotonin (5-HT) and choline acetyltransferase (ChAT) activity) and cortical EEG (quantitative EEG (qEEG) and high-voltage spindle (HVS)) activity in young and aged rats. Near complete 6-OHDA NA lesions, but not partial DSP-4 NA lesions, increased HVS activity in young rats. DSP-4 and 6-OHDA lesions produced no significant changes in the 5-HT or DA levels or in the ChAT activity in young rats. In some of the aged rats, DSP-4 produced similar biochemical and HVS effects, as it induced in young rats. In the remainder of the aged rats, NA levels were greatly and 5-HT levels slightly decreased. DA levels and ChAT activity were unaltered in either set of aged rats. HVS activity was increased only in that group of aged rats with the greatly lowered NA content. These results suggest that: (1) some of the aged rats are more sensitive to DSP-4 treatment than young adult rats; and (2) NA depletions have to be complete to produce an increase in HVS activity in young and aged rats.
MeSH Terms
- Aging
- Animals
- Benzylamines
- Brain Chemistry
- Choline O-Acetyltransferase
- Dopamine
- Electroencephalography
- Male
- Norepinephrine
- Oxidopamine
- Rats
- Rats, Inbred Strains
- Serotonin
- Sympathomimetics
Rat dentin contains a major sialic acid-rich glycoprotein, DSP, with an overall composition similar to that of bone sialoproteins but whose biological role in dentinogenesis is unknown. Using polyclonal affinity-purified antibodies to rat DSP and four immunohistochemical methods of detection, we studied the cell and tissue localization of DSP and the time course of its appearance during odontoblast differentiation. DSP first appeared within young odontoblasts concomitant with early secretion of pre-dentin matrix and before the onset of mineralization but was absent in pre-odontoblasts. DSP immunostaining also localized within secretory odontoblasts and was intense in odontoblastic processes. Early pre-dentin stained positive for DSP, in contrast to more mature pre-dentin, where immunoreactivity was less intense and more restricted to odontoblastic processes. In the zone of mineralized dentin matrix, a moderate and uniform staining pattern was evident. Intense immunostaining was also seen within the cells and matrix of dental pulp during dentinogenesis. Other cells and tissues within the tooth organ and those surrounding it were non-reactive. These findings suggest that DSP is developmentally expressed in cells of the odontoblastic lineage and may be a biochemical marker of odontoblastic activity.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Antibodies
- Cell Line
- Chromatography, Affinity
- Dentin
- Fluorescent Antibody Technique
- Immunoenzyme Techniques
- Immunohistochemistry
- Molecular Weight
- Odontoblasts
- Organ Specificity
- Rats
- Rats, Inbred Strains
- Sialoglycoproteins