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A J Patel

Publications and source records attributed to A J Patel.

137 records · Page 8Linked to original sources
PubMed1971

Effect of thyroid hormone on metabolic compartmentation in the developing rat brain.

1. The effects of treatment with thyroid hormone (tri-iodothyronine) and of neonatal thyroidectomy on the cerebral metabolism of [U-(14)C]leucine were investigated during the period of functional maturation of the rat brain extending from 9 to 25 days after birth. 2. Age-dependent changes in the labelling of brain constituents under normal conditions appear to depend on changes in the availability of blood-borne [(14)C]leucine resulting from differential rates of growth of body and brain; but developmental changes in the pool size of free leucine and in the rates of protein synthesis and oxidation of leucine are also involved. 3. Treatment with thyroid hormone had no significant effect on the conversion of leucine carbon into proteins and lipids; and the age-dependent changes in the concentration and specific radioactivity of leucine were similar to controls. On the other hand there was an acceleration in the conversion of leucine carbon into amino acids associated with the tricarboxylic acid cycle. These observations indicate that leucine oxidation was the process mainly affected. 4. The specific radioactivity of glutamine relative to that of glutamate was used as an index of metabolic compartmentation in brain tissue. Treatment with thyroid hormone advanced the development of metabolic compartmentation. 5. Neonatal thyroidectomy led to a marked decrease in the conversion of leucine carbon into proteins and lipids and to a significant increase in the amount of (14)C combined in the amino acids associated with the tricarboxylic acid cycle. The age-dependent increase in the glutamate/glutamine specific-radioactivity ratio was strongly retarded. 6. The increased conversion of leucine carbon into cerebral amino acids applied to glutamate and aspartate, but not to glutamine and gamma-aminobutyrate. This observation facilitated the understanding of the effects of thyroid deprivation on brain metabolism and provided new evidence for the allocation of morphological structures to the metabolic compartments in brain tissue. 7. In contrast with the marked effects of the thyroid state on metabolic compartmentation, it had relatively little effect on the developmental changes in the concentration of amino acids in the brain. 8. The rate of conversion of leucine carbon into the ;cycle amino acids' both under normal conditions and in thyroid deficiency indicated a special metabolic relationship between glutamate and aspartate on the one hand, and glutamine and gamma-aminobutyrate on the other.

Age Factors↗
PubMedDate not supplied

Thyroid deficiency and cell death in the rat cerebellum during development.

The [3H]-DNA content of the cerebellum remained constant during a period from 4 h to 8--9 days after the administration of [3H]-thymidine both to normal rats at 6 and 12 days of age and to thyroid deficient rats at 6 days. On the other hand, when [3H]-thymidine was given to 12-day-old thyroid deficient rats, a progressive decrease in the cerebellar content of [3H]-DNA was observed during the first 4 days after the injection. These findings, together with previous results showing a markedly elevated pyknotic index in the internal granular layer of the 12-day-old hypothyroid cerebellum, are consistent with there being an increased death of newly formed and differentiating granule cells in thyroid deficiency towards the end of the second week of postnatal life.

Animals↗
PubMedDate not supplied

Effects of haloperidol on cell proliferation in the early postnatal rat brain.

Haloperidol, a widely used neuroleptic, produced a significant depression of the rate of [3H]thymidine incorporation into the DNA of 11-day-old rat brain. The reduction of in-vivo DNA synthesis rate was detectable by 4 h after subcutaneous injection of a single dose of haloperidol (20 mg/kg) and through the period 10-24 h after drug treatment the rate was less than 50% of that of controls in the forebrain. [3H]Thymidine incorporation returned to control values by 32 h. The effect on the cerebellum was similar but less pronounced. The depression was dose-dependent and a half-maximal effect was produced with haloperidol doses of 5-10 mg/kg. Parallel histological studies on treated rats suggested prolongation of the DNA synthesis phase of the cell cycle in the forebrain subependymal layer, associated with an increase in turnover time of about 15%.

Animals↗