Protein amnionless precursor [Contains: Soluble protein amnionless] [UNQ513/PRO1028]
Metabotropic glutamate receptors (mGluRs) represent a potential therapeutic target. Possible anticonvulsant action of AMN 082, an agonist of mGluR7 subtype, was studied in immature rats using pentylenetetrazol (PTZ)-induced seizures as a model. Five age groups of rats (7-, 12-, 18-, 25-day-old and adult animals) were pretreated with AMN 082 in doses of 0.5, 1, 2, and 5 mg/kg i.p. and 30 min later PTZ was administered (100 mg/kg s.c.). Controls received saline instead of the agonist. AMN 082 did not exhibit clear anticonvulsant action with the exception of suppression of the tonic phase of generalized tonic-clonic seizures (GTCS) in 12-day-old rats. Shorter latencies of GTCS after AMN 082 pretreatment indicate a proconvulsant action. Involuntary movements (mostly tremor) appeared after AMN 082 before PTZ administration, therefore we performed another experimental series with AMN 082 only (1, 2, 5, and 10 mg/kg i.p.). During 60-min observation period tremor appeared in all age groups; sensitivity to this action decreased with age from the 2 mg/kg dose in 7- and 12-day-old rats to the 10 mg/kg dose in adult rats. Mixed anti- and proconvulsant actions of AMN 082 together with unwanted motor effects makes clinical use of this drug highly improbable.
- Age Factors
- Benzhydryl Compounds
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Excitatory Amino Acid Agonists
- Motor Activity
- Rats, Wistar
- Reaction Time
- Receptors, Metabotropic Glutamate
Intact and ovariectomized female rats were bilaterally lesioned in the anterior part of the medial amygdaloid nucleus (AMN) at 15, 21 or 26 days of age. The onset of puberty and the LH concentration in the peripheral serum on the third day after lesioning, respectively, were recorded. Damage to the AMN on day 15 induced a significant delay of vaginal opening and the first puberal ovulation and suppressed completely the castration-induced increase of LH secretion. In contrast, females lesioned on day 21 showed true precocious puberty and a significant elevation of the LH level as compared to the ovariectomized controls. The LH-inhibiting effect of s.c. administered estradiol benzoate (0.05 micrograms/100 g/day) was not diminished by lesions produced at this age. Neither the onset of puberty nor the LH concentration were influenced by lesioning of the AMN on day 26. Estimation of the LH concentration in untreated female rats revealed a distinct decline between 19 and 23 days of age followed by a significant increase between days 24 and 26. The findings indicate a transient LH-inhibiting activity of the medial amygdala in three-week-old female rats that is not related to the negative estrogen feedback. In other species, too, a temporary inhibitory action of the central nervous system may play a significant role in the prepuberal control of gonadotropin secretion.
- Luteinizing Hormone
- Sexual Maturation
The polyunsaturated fatty acid (PUFA) composition of the brain was studied in 8 patients with Zellweger's syndrome (ZS), 3 with neonatal adrenoleukodystrophy (NALD), one with bifunctional enzyme deficiency (BED), one with X-linked adrenoleukodystrophy (X-ALD), and one with adrenomyeloneuropathy (AMN). The PUFA composition of the liver, kidney and retina was studied in 8, 6 and 1 patients with ZS, respectively. An infant with NALD and a child with rhizomelic chondrodysplasia punctata (RCDP) were also studied for the PUFA composition of the liver. The liver and kidney of the patient with X-ALD and the liver of the patient with AMN were included in the study. The fatty acid values in the peroxisomal patients were compared with control data obtained in the normal developing brain (38 cases), liver (9 cases), kidney (7 cases) and retina (16 cases). The brain of a patient with metachromatic leukodystrophy (MLD) and the liver of a child with Krabbe's disease (KD) were also studied for comparison. The most constant and severe abnormality in all the peroxisomal patients was a drastic decrease in the total amount of docosahexaenoic acid (22:6 omega 3), especially in the brain. The other product of delta 4-desaturation, 22:5 omega 6, was generally decreased in the brain, liver and kidney of the ZS patients, but very much increased in the brain of two patients with NALD. The 22:6 omega 3/22:4 omega 6 ratio, which remains quite constant throughout normal brain development, was consistently decreased in the peroxisomal brain, in ZS as well as in NALD. This study confirms that, in classical Zellweger's syndrome, the two products of delta 4-desaturation are affected. In contrast, in neonatal adrenoleukodystrophy the deficiency is probably restricted to the omega 3 product of delta 4-desaturation, docosahexaenoic acid, especially in the brain, while the other product, 22:5 omega 6, is either normal or increased, perhaps in an attempt to compensate for the 22:6 omega 3 deficiency in brain membranes.
- Brain Chemistry
- Child, Preschool
- Chondrodysplasia Punctata
- Embryonic and Fetal Development
- Fatty Acids, Unsaturated
- Infant, Newborn
- Zellweger Syndrome