CBL
E3 ubiquitin-protein ligase CBL (EC 2.3.2.27) (Casitas B-lineage lymphoma proto-oncogene) (Proto-oncogene c-Cbl) (RING finger protein 55) (RING-type E3 ubiquitin transferase CBL) (Signal transduction protein CBL) [CBL2] [RNF55]
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Aging is associated with some cognitive decline and enhanced risk of development of neurodegenerative diseases. It is assumed that altered metabolism and functions of neurotrophin systems may underlie these age-related functional and structural modifications. CerebrolysinTM (CBL) is a neuropeptide mixture with neurotrophic effects, which is widely used for the treatment of stroke and traumatic brain injury patients. It is also evident that CBL has an overall beneficial effect and a favorable benefit-risk ratio in patients with dementia. However, the effects of CBL on cognition and brain neurotrophin system in normal aging remain obscure. The aim of the present study was to examine the age-related modifications of endogenous neurotrophin systems in the brain of male Wistar rats and the effects of CBL on learning and memory as well as the levels neurotrophins and their receptors. Old (23-24 months) and young (2-3 months) male Wistar rats were used for the study. A half of animals were subjected to CBL course (2.5 ml/kg, 20 i.p. injections). Behavior of rats was studied using the open field test and simple water maze training. The contents of NGF and BDNF were studied using enzyme-linked immunosorbent assay; the expression of neurotrophin receptors was estimated by Western-blot analysis. CBL treatment did not affect general status, age-related weight changes, general locomotor activity as well as general brain histology. In a water maze task, a minor effect of CBL was observed in old rats at the start of training and no effect on memory retention was found. Aging induced a decrease in neurotrophin receptors TrkA, TrkB, and p75NTR in the neocortex. CBL counteracted effects of aging on neocortical TrkA and p75NTR receptors and decreased expression of proNGF without influencing overall NGF levels. BDNF system was not significantly affected by CBL. The pro-neuroplastic "antiaging" effects of CBL in the neocortex of old animals were generally related to the NGF rather than the BDNF system.
MeSH Terms
- Age Factors
- Aging
- Amino Acids
- Animals
- Body Weight
- Brain
- Brain-Derived Neurotrophic Factor
- Exploratory Behavior
- Gene Expression Regulation
- Male
- Maze Learning
- Memory, Long-Term
- Nerve Growth Factor
- Neuroprotective Agents
- Rats
- Rats, Wistar
- Receptor, trkA
- Receptor, trkB
- Time Factors
Keywords
- Aging
- BDNF
- Cerebrolysin
- NGF
- TrkA
- TrkB
- brain
- hippocampus
- memory
- neocortex
- neurotrophin
- p75NTR
- rat
The purpose is to determine the effects of 6 months caloric restriction and aerobic training (3x/wk) (CR AEX) on c-CBL associated protein (CAP) gene expression in women with a history of GDM. CAP is involved in cell signaling and protein ubiquitination, and is linked to the development of insulin resistance. Obese (BMI=32 ± 1 kg/m , % fat=46 ± 2, X ± SEM), sedentary (VO2 max=21.2 ± 1.2 ml/kg/min), women aged 52 ± 2 years participated in 6 months D WL (n=10) with body composition, fitness (VO2 max), and glucose tolerance testing. Insulin sensitivity was assessed during the last 30 min of 2-hour hyperinsulinemic-euglycemic clamps (40 mU.m .min ) pre and post interventions. Vastus lateralis skeletal muscle biopsies (n=7) were conducted and CAP, GLUT4 and glycogen synthase (GS) gene expression measured by RT-PCR. No change in FFM by DXA was observed, but body weight decreased 8% with losses of total body fat mass (P<0.05) and a 10% increase in VO2 max (P<0.01). Glucose and insulin areas under the curve by OGTT decreased (P<0.05). Glucose utilization during the clamp increased 27% (23.1 ± 3.8 vs. 29.4 ± 3.6 umol.kg.min , P<0.05). Vastus lateralis skeletal muscle CAP expression increased 21% (P<0.05) but GLUT4 did not. Results suggest that changes in CAP could be involved in the improvement in glucose metabolism with caloric restriction and aerobic training in women with a history of gestational diabetes.
Keywords
- Aging
- Exercise
- Gestational diabetes
- Insulin signaling
- Nutrition
- Obesity
Neurotrophic factors are currently being considered as pro-cognitive therapeutic approaches for management of cognitive deficits. This study aims to evaluate the effects of intranasal (i.n.) or intraperitoneal (i.p.) administration of Cerebrolysin (CBL) (as a mixture of neurotrophic factors) on the d-galactose-induced oxidative stress, apoptosis and memory as well as learning impairment in mice. For this purpose, CBL (1, 2.5, 5 ml/kg/i.p.) or (1 ml/kg/i.n.), were administrated daily in d-galactose-received (100 mg/kg/subcutaneous (s.c.)) mice model of aging for eight weeks. Spatial and recognition memories were assessed by the Morris water maze and novel object recognition tasks. Brain and blood of animals were analysed for oxidative stress biomarkers including malondialdehyde, total antioxidant capacity, glutathione peroxidase and superoxide dismutase. Apoptosis rate in the hippocampus was evaluated by TUNEL staining of brain tissue. 5 ml/kg/i.p. dose of CBL increased the locomotor activity but, 1 ml/kg/i.p. dose didn't show detectable behavioural or molecular effects on aged mice. Treatment with 2.5 ml/kg/i.p. and 1 ml/kg/i.n. doses attenuated d-galactose-impaired spatial and recognition memories. Results showed an obvious increase in the antioxidant biomarkers and decrease in the malondialdehyde levels both in the blood and brain of aged mice in 2.5 ml/kg/i.p. dose, and only in the brain in 1 ml/kg/i.n. dose of CBL. Anti-apoptotic effects also were seen in the same dose/rout of CBL administration in aged animals. This study proves the usefulness of i.n. CBL administration as a non-invasive and efficient method of drug delivery to the brain to improve aging-induced oxidative stress, apoptosis and learning as well as memory impairment.
MeSH Terms
- Administration, Intranasal
- Aging
- Amino Acids
- Animals
- Apoptosis
- Biomarkers
- Cognitive Dysfunction
- Disease Models, Animal
- Galactose
- Hippocampus
- Male
- Maze Learning
- Memory
- Memory Disorders
- Mice
- Mice, Inbred BALB C
- Neuroprotective Agents
- Oxidative Stress
Keywords
- Cerebrolysin
- D-galactose
- Intranasal
- Learning
- Memory
- Senescence
Tauopathies are a group of neurodegenerative disorders with accumulation of three-repeat (3R) or four-repeat (4R) Tau. While 3R tau is found in Pick's disease and Alzheimer's disease (AD), 4R tau is more abundant in corticobasal degeneration, progressive supranuclear palsy, and AD. We have previously shown that Cerebrolysin™ (CBL), a neuropeptide mixture with neurotrophic effects, ameliorates the pathology in amyloid precursor protein transgenic (tg) mouse model of AD and 4R tau, however it is unclear if CBL ameliorates the deficits and neuropathology in the mouse model of Pick's disease over expressing 3R tau. Mice expressing 3R tau (L266V and G272V mutations) under the mThy-1 promoter were treated with CBL in two separate groups, the first was 3 months old (treated for 3 months, IP) and the second was 6 months old (treated for 3 months, IP) at the start of the treatment. We found that although the levels of total 3R tau were unchanged, CBL reduced the levels of hyper-phosphorylated tau in both groups of mice. This was accompanied by reduced neurodegenerative pathology in the neocortex and hippocampus in both groups and by improvements in the behavioral deficits in the nest-building test and water maze in the 3-6 month group. Taken together these results support the notion that CBL may be beneficial in other taupathy models by reducing the levels of aberrantly phosphorylated tau.
MeSH Terms
- Aging
- Amino Acids
- Animals
- Cerebral Cortex
- Disease Models, Animal
- Glycogen Synthase Kinase 3
- Glycogen Synthase Kinase 3 beta
- Hippocampus
- Humans
- Mice, Inbred C57BL
- Mice, Transgenic
- Mutation
- Neuroprotective Agents
- Phosphorylation
- Pick Disease of the Brain
- Proto-Oncogene Proteins c-akt
- Tauopathies
- tau Proteins
Cerebrolysin® (CBL) is a neuroprotective drug used for the treatment of neurodegenerative diseases. CBL's mechanisms of action remain unclear. Involvement of tryptophan (TRP)-kynurenine (KYN) pathway in neuroprotective effect of CBL might be suggested considering that modulation of KYN pathway of TRP metabolism by CBL, and protection against eclosion defect and prolongation of life span of Drosophila melanogaster with pharmacologically or genetically-induced down-regulation of TRP conversion into KYN. To investigate possible involvement of TRP-KYN pathway in mechanisms of neuroprotective effect of CBL, we evaluated CBL effects on metamorphosis and life span of Drosophila melanogaster maintained at 23 °C and 28 °C ambient temperature. CBL accelerated metamorphosis, exerted strong tendency ([i]p[/i] = 0.04) to prolong life span in female but not in male flies, and attenuated aging-accelerating effect of high (28 °C) ambient temperature in both female and male flies. Further research of CBL effects on metamorphosis and resistance to aging-accelerating effect of high temperature might offer new insights in mechanisms of its neuroprotective action and expand its clinical applications.
Keywords
- Aging
- Cerebrolysin
- Drosophila
- Eclosion
- High Temperature
- Kynurenine
- Life Span
- Metamorphosis
- Neuroprotection
- Tryptophan
Alzheimer's Disease (AD) and Fronto temporal lobar dementia (FTLD) are common causes of dementia in the aging population for which limited therapeutical options are available. These disorders are associated with Tau accumulation. We have previously shown that Cerebrolysin™ (CBL), a neuropeptide mixture with neurotrophic effects, ameliorates the behavioral deficits and neuropathological alterations in amyloid precursor protein (APP) transgenic (tg) mouse model of AD by reducing hyper-phosphorylated Tau. CBL has been tested in clinical trials for AD, however it's potential beneficial effects in FTLD are unknown. For this purpose we sought to investigate the effects of CBL in a tg model of tauopathy. Accordingly, double tg mice expressing mutant Tau under the mThy-1 promoter and GSK3β (to enhance Tau phosphorylation) were treated with CBL and evaluated neuropathologically. Compared to single Tau tg mice the Tau/GSK3β double tg model displayed elevated levels of Tau phosphorylation and neurodegeneration in the hippocampus. CBL treatment reduced the levels of Tau phosphorylation in the dentate gyrus and the degeneration of pyramidal neurons in the temporal cortex and hippocampus of the Tau/GSK3β double tg mice. Interestingly, the Tau/GSK3β double tg mice also displayed elevated levels of Dynamin-related protein-1 (Drp-1), a protein that hydrolyzes GTP and is required for mitochondrial division. Ultrastructural analysis of the mitochondria in the Tau/GSK3β double tg mice demonstrated increased numbers and fragmentation of mitochondria in comparison to non-tg mice. CBL treatment normalized levels of Drp-1 and restored mitochondrial structure. These results suggest that the ability of CBL to ameliorate neurodegenerative pathology in the tauopathy model may involve reducing accumulation of hyper-phosphorylated Tau and reducing alterations in mitochondrial biogenesis associated with Tau.
MeSH Terms
- Aging
- Amino Acids
- Animals
- Disease Models, Animal
- Dynamins
- Glycogen Synthase Kinase 3
- Glycogen Synthase Kinase 3 beta
- Hippocampus
- Mice, Inbred C57BL
- Mice, Inbred DBA
- Mice, Transgenic
- Mitochondria
- Neuroprotective Agents
- Phosphorylation
- Pyramidal Cells
- Tauopathies
- Temporal Lobe
- tau Proteins
Evidence from model organisms suggests that the insulin/IGF-1 signaling pathway has an important, evolutionarily conserved influence over rate of aging and thus longevity. In humans, the FOXO3 gene is the only widely replicated insulin/IGF-1 signaling pathway gene associated with longevity across multiple populations. Therefore, we conducted a nested case-control study of other insulin/IGF-1 signaling genes and longevity, utilizing a large, homogeneous, long-lived population of American men of Japanese ancestry, well characterized for aging phenotypes. Genotyping was performed of single nucleotide polymorphisms, tagging most of the genetic variation across several genes in the insulin/IGF-1 signaling pathway or related gene networks that may be influenced by FOXO3, namely, ATF4, CBL, CDKN2, EXO1, and JUN. Two initial, marginal associations with longevity did not remain significant after correction for multiple comparisons, nor were they correlated with aging-related phenotypes.
MeSH Terms
- Activating Transcription Factor 4
- Aged, 80 and over
- Aging
- Asian Americans
- Case-Control Studies
- Cohort Studies
- DNA Repair Enzymes
- Exodeoxyribonucleases
- Forkhead Box Protein O3
- Forkhead Transcription Factors
- Gene Frequency
- Genes, jun
- Genes, p16
- Genetic Variation
- Genotype
- Humans
- Insulin
- Insulin Resistance
- Insulin-Like Growth Factor I
- Japan
- Longevity
- Longitudinal Studies
- Male
- Polymorphism, Genetic
- Polymorphism, Single Nucleotide
- Proto-Oncogene Proteins c-cbl
- Signal Transduction
Keywords
- Human.
- Insulin signaling genes
- Longevity
- Molecular genetics
Controlled hypotension is routinely used during open repair of craniosynostosis to decrease blood loss, although this benefit is unproven. In this study the authors analyzed the longitudinal relationships between intraoperative mean arterial pressure (MAP) and calculated blood loss (CBL) during frontoorbital advancement (FOA) for craniosynostosis. The authors reviewed the records of infants with craniosynostosis who had undergone primary FOA between 1997 and 2009. Anesthesia records provided preoperative and serial intraoperative MAP. Interval measures of CBL had been determined during the course of the operation. The longitudinal relationships between MAP(mean), MAP(change), and CBL(change) were assessed over the same time interval and compared between adjacent time intervals to determine the directionality of associations. Ninety infants (44 males and 46 females) underwent FOA at a mean age and weight of 10.7 ± 12.9 months and 9.0 ± 7.0 kg, respectively. The average intraoperative MAP was 56.1 ± 4.8 mm Hg, 22.6 ± 12.1% lower than preoperative baseline. A negative correlation was found between CBL(change) and MAP(mean) over the same interval (r = -0.31, p < 0.05), and an inverse relationship was noted between CBL(change) of the previous interval and MAP(change) of the next interval (r = -0.07, p < 0.05). Finally, there was no significant association between MAP(change) of the previous interval and CBL(change) of the next interval. Calculated blood loss demonstrated a negative correlation with MAP during FOA. Directionality testing indicated that MAP did not affect intraoperative blood loss; instead, blood loss drove changes in MAP. Overall, these findings challenge the benefit of controlled hypotension during open craniofacial repair.
MeSH Terms
- Aging
- Algorithms
- Blood Loss, Surgical
- Blood Pressure
- Craniosynostoses
- Female
- Frontal Bone
- Hemoglobins
- Humans
- Hypotension, Controlled
- Infant
- Intraoperative Care
- Longitudinal Studies
- Male
- Neurosurgical Procedures
- Orbit
Casitas B-cell lymphoma (Cbl)-family E3 ubiquitin ligases are negative regulators of tyrosine kinase signaling. Recent work has revealed a critical role of Cbl in the maintenance of hematopoietic stem cell (HSC) homeostasis, and mutations in CBL have been identified in myeloid malignancies. Here we show that, in contrast to Cbl or Cbl-b single-deficient mice, concurrent loss of Cbl and Cbl-b in the HSC compartment leads to an early-onset lethal myeloproliferative disease in mice. Cbl, Cbl-b double-deficient bone marrow cells are hypersensitive to cytokines, and show altered biochemical response to thrombopoietin. Thus, Cbl and Cbl-b play redundant but essential roles in HSC regulation, whose breakdown leads to hematological abnormalities that phenocopy crucial aspects of mutant Cbl-driven human myeloid malignancies.
MeSH Terms
- Adaptor Proteins, Signal Transducing
- Aging
- Animals
- Cell Proliferation
- Hematopoietic Stem Cells
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Myeloproliferative Disorders
- Proto-Oncogene Proteins c-cbl
- Thrombopoietin
- Time Factors
Rett syndrome is a childhood neurodevelopmental disorder caused by mutations in the gene encoding for methyl-CpG-binding protein (MeCP2). Neuropathological studies in patients with Rett syndrome and in MeCP2 mutant models have shown reduced dendritic arborization and abnormal neuronal packing. We have previously shown that Cerebrolysin (CBL), a neurotrophic peptide mixture, ameliorates the synaptic and dendritic pathology in models of aging and neurodegeneration. This study aimed to determine whether CBL was capable of reducing behavioral and neuronal alterations in Mecp2(308/Y) mutant mice. Two sets of experiments were performed, the first with 4-month-old male Mecp2(308/Y) mutant mice treated with CBL or vehicle for 3 months (Group A) and the second with 1-month-old mice treated for 6 months (Group B). Behavioral analysis showed improved motor performance with CBL in Group A and a trend toward improvement in Group B. Consistent with behavioral findings, neuropathological analysis of the basal ganglia showed amelioration of dendritic simplification in CBL-treated Mecp2(308/Y) mutant mice. CBL treatment also ameliorated dendritic pathology and neuronal loss in the hippocampus and neocortex in Mecp2(308/Y) mutant mice. In conclusion, this study demonstrates that CBL promotes recovery of dendritic and neuronal damage and behavioral improvements in young adult Mecp2(308/Y) mutant mice and suggests that CBL may have neurotrophic effects in this model. These findings support the possibility that CBL may have beneficial effects in the management of Rett syndrome.
MeSH Terms
- Acetylation
- Aging
- Amino Acids
- Animals
- Dendrites
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Hippocampus
- Histones
- Male
- Methyl-CpG-Binding Protein 2
- Mice
- Mice, Transgenic
- Mutation
- Neocortex
- Nerve Degeneration
- Nootropic Agents
- Rett Syndrome
- Synapses
The DWR Department of Geriatric Medicine at OUHSC and the OKC VA Medical Center began a mandatory third-year geriatric medicine clerkship in 2003. As part of the didactic sessions, the Department created a longitudinal Case-Based Learning (CBL) experience. The purpose of this paper is to describe the CBL experience, report student satisfaction with the CBL process, and discuss how students value CBL as a teaching method compared to other methods. The results indicate that CBL is highly valued among the students due to the interactive nature of the sessions and longitudinal nature of the cases.
MeSH Terms
- Clinical Clerkship
- Geriatrics
- Humans
- Problem-Based Learning
- Program Development
- Program Evaluation
The purpose of this study was to investigate nursing students' knowledge of and attitudes toward older adults in the first and fourth years of a baccalaureate program, following the introduction of a context-based learning (CBL) curriculum, and to compare the fourth-year CBL student findings to those of fourth-year students in the final year of the traditional, lecture-based baccalaureate program. The Facts on Aging Questionnaire was used to assess knowledge, and the Aging Semantic Differential was used to assess attitudes toward aging related to societal influences. Although there were differences in knowledge and attitudes between fourth-year CBL and fourth-year traditional students, the differences were not significant. These findings support earlier work that an integrated curriculum may not significantly improve knowledge of age-related changes nor positively influence attitudes that are already positive. The Reactions to Ageing Questionnaire was used to examine students' attitudes toward personal aging. There was a significant positive increase in CBL students' attitudes toward personal aging from the first to fourth years of the program. This suggests that CBL learning fosters an inner maturity toward personal aging.
MeSH Terms
- Adult
- Aged
- Aging
- Alberta
- Attitude of Health Personnel
- Clinical Competence
- Cross-Sectional Studies
- Curriculum
- Education, Nursing, Baccalaureate
- Female
- Geriatric Nursing
- Health Knowledge, Attitudes, Practice
- Humans
- Longitudinal Studies
- Male
- Nursing Education Research
- Nursing Methodology Research
- Prejudice
- Problem-Based Learning
- Program Evaluation
- Semantic Differential
- Students, Nursing
- Surveys and Questionnaires
The expression of brain-derived neurotrophic factor (BDNF) mRNA and the secretion of BDNF protein are tightly regulated by neuronal activity. Thus, BDNF has been proposed as a mediator of activity-dependent neural plasticity. Previous studies showed that dark rearing (DR) reduces BDNF mRNA levels in the primary visual cortex (V1), but the effects of visual experience on BDNF protein levels are unknown. We report that rearing in constant light or DR alters BDNF mRNA and protein levels in the retina, superior colliculus (SC), V1, hippocampus (HIPP), and cerebellum (CBL), although the changes in mRNA and protein are not always correlated. Most notably, DR increases BDNF protein levels in V1 although BDNF mRNA is decreased. BDNF protein levels also undergo diurnal changes. In the retina, V1, and SC, BDNF protein levels are higher during the light phase of the circadian cycle than during the dark phase. By contrast, in HIPP and CBL, the tissue concentration of BDNF protein is higher during the dark phase. The discrepancies between the experience-dependent changes in BDNF mRNA and protein suggest that via its effects on neuronal activity, early sensory experience alters the trafficking, as well as the synthesis, of BDNF protein. The circadian changes in BDNF protein suggest that BDNF could cause the diurnal modulation of synaptic efficacy in some neural circuits. The fluctuations in BDNF levels in nonvisual structures suggest a potential role of BDNF in mediating plasticity induced by hormones or motor activity.
MeSH Terms
- Aging
- Animals
- Brain-Derived Neurotrophic Factor
- Cerebellum
- Circadian Rhythm
- Cricetinae
- Darkness
- Hippocampus
- Light
- Mesocricetus
- Neuronal Plasticity
- Photic Stimulation
- RNA, Messenger
- Rats
- Rats, Long-Evans
- Retina
- Superior Colliculi
- Visual Cortex
- Visual Pathways
The development of antigen-specific functional T lymphocyte immunity in infants and children is an area of immunology that needs elucidation. Leukocytes from cord blood (CBL) and from PBL of children of different ages who were in the hospital for minor surgical procedures were compared with PBL from healthy adults for their ability to generate T helper cell (Th) responses assessed by in vitro proliferation and IL-2 production after stimulation with: influenza A virus (FLU); tetanus toxoid (TET); adult allogeneic PBL that were either undepleted (ALLO) or depleted of adherent antigen presenting cells (ALLONW); and PHA. CBL generated Th responses to ALLONW, ALLO, and PHA, but not to FLU or TET. PBL from infants between 6 and 13 mo of age responded to ALLO and PHA; none responded to FLU or ALLONW, and two of four responded weakly to TET. PBL from children between 13 and 26 mo of age responded to all stimuli except FLU, to which only one child responded marginally. PBL from children older than 36 mo responded to all stimuli at levels comparable to those of PBL from adults. The use of undepleted and adherent cell-depleted CBL and PBL from children of different ages as allogeneic stimulators of responses generated by PBL from adults indicated that the antigen presenting function of CBL and PBL from children 13 mo or older are sufficiently developed to present alloantigen, whereas PBL from children younger than 13 mo are not. Therefore, our results indicate that age-dependent differences exist in both T helper and antigen-presenting functions of CBL and PBL from children of different ages. Surprisingly, CBL appear to be more efficient in antigen-presenting function than PBL from children younger than 13 mo. These findings are important for establishing developmental parameters of T helper cell immunity relevant for pediatric infection and transplantation in infants and children.
MeSH Terms
- Adult
- Aging
- Antigen-Presenting Cells
- Child, Preschool
- Fetal Blood
- Fetus
- Humans
- Infant
- Interleukin-2
- Lymphocyte Activation
- Orthomyxoviridae
- T-Lymphocytes, Helper-Inducer
- Tetanus Toxoid
- Time Factors
- Transplantation, Homologous
Expression of CD45R0 antigen has been evaluated on the surface of T lymphocyte subsets obtained from cord blood and on peripheral blood lymphocytes (PBL) from both term and preterm neonates. In some experiments, expression of the same antigen has also been evaluated after in vitro activation of cord blood lymphocytes (CBL) with phytohemagglutinin (PHA) or in mixed lymphocyte culture. The CD45R0 molecule was found to be present on a significantly lower percentage of CD3 , CD4 and CD8 CBL as compared with the same subsets evaluated in adult individuals. Moreover, at variance with adult PBL, the great majority of CBL displayed a low level of fluorescence when stained with UCHL1 (CD45R0-specific monoclonal antibody), and both PHA and allogeneic stimuli were able to strongly increase the expression of the CD45R0 molecule on CBL. The percentage of CD45R0 PBL obtained from both term and preterm neonates on the 1st day of life was comparable to that of CBL, however the expression of this molecule increases remarkably within a few days in the majority of term neonates, while it seems to take more time for the antigen to be fully expressed in preterm infants.
MeSH Terms
- Aging
- Fetal Blood
- Humans
- Immunophenotyping
- Infant, Newborn
- Infant, Premature
- Leukocyte Common Antigens
- Lymphocyte Activation
- T-Lymphocyte Subsets
The age-dependent changes in the surface electrical charge of human peripheral blood lymphocytes were analyzed by establishing the differences between the surface density of four types of chemical groups on lymphocytes isolated from the blood of individuals of increasing ages. Similar determinations were carried out on cord blood lymphocytes which were shown previously to exhibit either a low or a high electrical charge density reflected in the experimentally determined parameter, the anodic electrophoretic mobility (EPM), differing by about 30%. The surface density of carboxyl group of N-acetylneuraminic acid (NANA), protein side chain epsilon-amino groups, and phosphate groups were different for the two subpopulations of CBL. Differences were also observed between the surface density of these groups on the two subpopulations of CBL and the lymphocytes of older individuals, with the exception of carboxyl groups. In some experiments on lymphocytes from adults, the carboxyls of NANA were much more numerous on nearly 1% of the cells.
MeSH Terms
- Adult
- Aged
- Aging
- Amines
- Cations
- Cell Membrane
- Child
- Child, Preschool
- Electrochemistry
- Electrophoresis
- Humans
- Infant
- Infant, Newborn
- Lymphocytes
- Middle Aged
- Phosphates
- Sialic Acids
The development of catecholaminergic and cholinergic neurones in the cat's retina has been examined with antibodies against their respective rate-limiting enzymes, tyrosine hydroxylase (TH) and choline acetyl transferase (ChAT). ChAT-immunoreactive (IR) cells were first detected at E (embryonic day) 56 with somata in the ganglion cell layer (GCL) or in the inner cytoblast layer (CBL). At P (postnatal day) 1, two faint bands of ChAT-IR fibres were evident in an inner and outer strata of the inner plexiform layer (IPL) and by P26, the bands were similar to those in the adult. TH immunoreactivity was first detected at E59 in either darkly labelled somata in the inner CBL with processes extending toward the IPL or in lightly labelled somata also located in CBL but with no processes. At P1, most TH-IR cells had prominently labelled dendrites and, by P8, most of the features of the adult cells were evident. Soma size gradients among TH-IR cells were first detected at P8, with cells in temporal retina being larger than those in nasal retina or at the area centralis. The smaller sizes of cells at the area centralis emerged after P26. The smaller sizes of ChAT-IR somata at the area centralis, by contrast, emerged between P8 and P26. The number of both TH-IR and ChAT-IR cells declined from the time they first appeared till adulthood. The decline was smaller among ChAT-IR cells (24%) than among TH-IR cells (68%). In distribution, the differential expansion of the retina appeared to be largely responsible for generating the final adult distribution of ChAT-IR cells. However, during late postnatal development (P26 to adulthood), the density of ChAT-IR cells in the periphery declined more than that of the ganglion cells, suggesting that some ChAT-IR cells may die in the periphery during this time. Prior to P26, the changes in the distribution of TH-IR cells were inconsistent with the pattern of retinal expansion. It is suggested that during this period, regional cell loss and cell addition may account for the changes in distribution of TH-IR cells. Later in development (P26 to adulthood), the changes in the density of TH-IR cells closely conformed to the differential expansion of the retina.
MeSH Terms
- Aging
- Animals
- Catecholamines
- Cats
- Cell Count
- Choline O-Acetyltransferase
- Cholinergic Fibers
- Embryonic and Fetal Development
- Immunohistochemistry
- Retina
- Tyrosine 3-Monooxygenase
Although Syrian hamsters and Mongolian gerbils are closely related, they have quite different patterns of retinal ganglion cell distribution and different patterns of retinal growth that produce their distributions. We have examined the morphology and distribution of catecholaminergic (CA) neurones in adult and developing retinae of these species in order to gain a more general understanding of the mechanisms producing cellular topographies in the retina. CA neurones were identified with an antibody to tyrosine hydroxylase (TH), the rate limiting enzyme in the production of catecholamines. In adult retinae of both hamsters and gerbils, most CA somata were located in the inner part of the inner nuclear layer (INL) and CA dendrites spread in a outer stratum of the inner plexiform layer (IPL). Their somata varied with retinal position, being largest in temporal and smallest in central retina. In hamsters, but not gerbils, a small number of CA interplexiform cells was also observed. In development, CA somata of hamster retinae were observed first in the middle and/or scleral regions of the cytoblast layer (CBL) at P (postnatal day) 8. By P12, CA somata were commonly located in the inner part of the INL and their dendrites spread into the outer region of the IPL. In developing gerbil retinae, CA somata were first observed at P6 in the middle of the CBL. Over subsequent days, they migrated into the inner part of the INL and spread their dendrites into the outer strata of the IPL. In both hamsters and gerbils, CA cells were initially concentrated in the superior temporal margin of the retina. In hamsters, this supero-temporal concentration persisted until adulthood, whereas in adult gerbils, the greatest density of CA cells was found just superior to the visual streak. These distributions were distinct from those of the ganglion cells in adult and developing retinae of each species. We discuss the role of maturational expression of TH, cell death, and retinal growth in the generation of the distinct distribution of the CA cells.
MeSH Terms
- Aging
- Animals
- Catecholamines
- Cricetinae
- Gerbillinae
- Immunohistochemistry
- Mesocricetus
- Retina
- Tyrosine 3-Monooxygenase