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Biomedical subjects

A J Patel

Publications and source records attributed to A J Patel.

At least 109 records · Page 6Linked to original sources
PubMed1980

Effect of chlorpromazine on cell proliferation in the developing rat brain. A combined biochemical and morphological study.

Chlorpromazine, a widely used drug in current clinical practice, produced a severe reduction of the rate of [3H]thymidine incorporation into brain DNA of 11-day-old rats. The depression of in vivo synthesis rate was detectable by 6 h after chlorpromazine administration (50 mg/kg, s.c.) and the rate was less than 40% and 60% of controls during period 14-30 h in forebrain and 6-30 h in cerebellum respectively. The depression was dose-dependent and half maximal effect was produced with about 10 mg/kg chlorpromazine. The drug caused some retardation in the rate of conversion of [3H]thymidine to [3H]thymine nucleotides in the brain, but the severe depression in DNA labelling was also evident after correcting the values on the basis of [3H]thymine nucleotides concentration. Mitotic activity was significantly reduced in the cerebellar external granular layer. Increased numbers of cell degenerations, shown by Feulgen cytophotometry to be postmitotic, were seen in both layers 12 and 32 h after chlorpromazine. Analysis of cell cycle parameters showed no significant changes. However, the labelling index in subependymal cells was reduced, indicating an increase in turnover time of about 40%. The results are consistent with an action of chlorpromazine on cell proliferation, either by direct effects on the generation and survival of cells, or via its major pharmacological actions on neurotransmitter balance. These effects are potentially of functional and clinical significance.

Age Factors↗
PubMed1980

Effects of undernutrition on gliogenesis and glial maturation in rat corpus callosum.

Rats were undernourished by halving the mother's food intake from the sixth day of pregnancy onwards and through lactation. At weaning, the young rats were restricted to half the normal weight of food. A combination of light and electron microscopic techniques was used to study the effects of this regime on gliogenesis and glial maturation in the corpus callosum of animals aged between 15 and 48 days. A disturbance of neuroglial proliferation was suggested by the finding of an increased proportion of astroglia relative to oligodendroglia in the 15-day-old undernourished rats, indicating a delay in the acquisition of cells produced relatively late in development. Impaired differentiation of oligodendroglia was suggested by the finding in treated animals of increased light oligodendrocytes at 15 days and a deficit of dark oligodendrocytes at 48 days, relative to controls. The previously observed retardation in myelin acquisition seems thus to be related to a delay in the differentiation of oligodendroglia, although it seems likely that the proliferation of these cells is also disturbed in undernutrition.

Animals↗
PubMed1980

Effects of thyroid state on brain development: beta-adrenergic receptors and 5'-nucleotidase activity.

The effect of thyroid status on beta-adrenergic receptor binding and 5'-nucleotidase activity was studied in the forebrain and the cerebellum of the rat during the first 5 postnatal weeks. The developmental increase in beta-adrenergic receptor binding was significantly depressed in thyroid deficiency in both the forebrain and the cerebellum. The effect was more pronounced in the cerebellum, where at day 35 the concentration and the total number of beta-adrenergic receptor sites were reduced by 35% and 50% respectively. In contrast, hyperthyroidism had no significant effect on the development of beta-adrenergic receptors in the brain. On the other hand, hyperthyroidism led to a sustained increase in the forebrain in the activity of 5'-nucleotidase, an enzyme which is also associated with plasma membranes and has been proposed to play some role in neurotransmission. In thyroid deficiency the enzyme activity was markedly depressed. The effect was significant from day 12 in the cerebellum and from day 21 in the forebrain, the maximal depression, at day 21, being 55% and 45% respectively. In comparison with these plasma membrane markers, the accretion of membranous proteins was less affected: although this was retarded in hypothyroidism and advanced in hyperthyroidism there was no residual effect at 35 days except those attributable to changes in organ size. The results indicated, therefore, that the biochemical specialization of cells, as reflected in certain plasma membrane constituents, are chatacteristically influenced in the developing brain by thyroid disorders.

Aging↗
PubMed1980

Effects of thyroid state on brain development: muscarinic acetylcholine and GABA receptors.

A study was made of the effects of age, neonatal hypothyroidism and hyperthyroidism on the development in rat brain of muscarinic cholinergic and GABA receptors. The former receptors were estimated by the binding of [3H]quinuclidinylbenzilate and the latter by binding of [3H]muscimol to crude membrane preparations from the forebrain and the cerebellum. In the normal forebrain, the density of muscarinic cholinergic receptors (in terms of unit membrane proteins) doubled during the period 6-35 days after birth. Thyroid state had relatively little effect on this development. In contrast, in the normal cerebellum the peak of the density of the receptors was attained in the early neonatal period followed by a progressive decline reaching about half of the maximum at day 35. Furthermore, in the cerebellum this development was significantly influenced by thyroid disorders: the rate of decrease in receptor density was accelerated by hyperthyroidism and retarded in thyroid deficiency. In comparison with euthyroid rats, the density of muscarinic receptors in the cerebellum was 30% lower in the hyperthyroidism (at day 21) and 40% higher in thyroid deficiency (at day 35). The increase in the density of GABA receptors with age was very small in the normal forebrain relative to the marked rise in the cerebellum. In the forebrain, thyroid state had no significant effect on this development. In contrast, in the cerebellum the ontogenesis of GABA receptors was advanced by thyroid hormone treatment and retarded in thyroid deficiency. However, by day 35 receptor density was normal in both conditions. Thyroid state had no significant influence on the affinity of either [3H]muscimol or the [3H]quinuclidinylbenzilate binding. The results suggest that thyroid hormone disorders during early life may lead to distortions rather than synchronized shifts in the relative development of several central transmitter systems.

Acetylcholine↗
PubMed1980

Distribution of GABA receptors in the rat cerebellum.

The distribution of GABA receptors in the cerebellum is not homogeneous. In comparison with detergent-treated membranes from the whole tissue the number of [3H]muscimol binding sites per mg protein (Bmax) is about doubled in preparations enriched in large fragments of the cerebellar glomeruli, and it is about one-third in the dissected deep nuclei. On the other hand, the apparent affinity (Kd) is similar in the different preparations. Comparison of the results with earlier studies suggests a heterogeneity in cerebellar GABA receptors and/or their control.

Animals↗
PubMed1980

Effects of albumin, amino acids, and clofibrate on the uptake of tryptophan by the rat brain.

The influences of total tryptophan concentration, albumin binding, and amino acid competition on the rate of tryptophan influx into rat brain were compared using a single-pass injection technique with tritiated water as a freely diffusible reference. Omission of 3% bovine albumin froma bolus containing tryptophan in Krebs-Ringer bicarbonate buffer injected into the carotid artery increased non-albumin bound (free) tryptophan concentration threefold but tryptophan uptake by only 35% and 30% into forebrain and hypothalamus, respectively. However, tryptophan uptake from injected rat plasma was more markedly elevated when free tryptophan concentration was raised. Thus, when free tryptophan was doubled, but total tryptophan unchanged, by in vitro addition of clofibrate to a plasma bolus, uptake was increased by 53% and 28% into forebrain and hypothalamus respectively. When clofibrate was injected in vivo so that plasma total tryptophan concentration was decreased by 45% but neither free tryptophan nor competing amino acid concentrations were altered, then uptake from a bolus of the rat's own plasma was unchanged. Addition of competing amino acids at physiological concentrations to tryptophan in Krebs-Ringer buffer significantly reduced tryptophan influx into both brain regions, but did not increase the effect of albumin binding. The results indicate that tryptophan uptake into rat forebrain is substantially influenced by albumin binding and competition from other amino acids, but that hypothalamic uptake is less influenced by these factors.

Amino Acids↗
PubMed1979

Effects of thyroxine on postnatal cell acquisition in the rat brain.

The effects of treatment with L-thyroxine (3 micrograms by subcutaneous injection daily from birth) on cell acquisition in the rat brain were studied during the first 3 postnatal weeks. In the forebrain, thyroxine has no effect on cell proliferation in the first 6 days, but it causes decreased cell acquisition from 12 to 21 days so that cell number becomes significantly reduced. Estimates of cell proliferation kinetics and of cell death in the lateral ventricular subependymal layer show no apparent abnormality. In the cerebellum, treatment from birth leads to increased cell proliferation during the first week: in comparison with controls, the rate of [3H]thymidine incorporation into DNA, thymidine kinase activity, and the number of cells both in the major germinal site (external granular layer: EGL) and in the whole cerebellum are elevated. This initial effect of thyroxine appears by day 3 and is short-lived, being no longer evident after day 6. The build-up of cell numbers in the EGL at day 6 seems to be related to a preceding, transient retardation of cell migration from this layer rather than to an acceleration of cell replication, since cell cycle parameters are normal. From day 12 the rate of [3H]thymidine incorporation into DNA is severely reduced in treated rats. Advancement of cellular differentiation rather than increased cell death in the EGL appears to be involved in this phenomenon.

Aging↗
PubMed1979

Effect of thyroid deficiency on the growth of the hippocampus in the rat. A combined biochemical and morphological study.

The growth of the hippocampus was studied in normal and hypothyroid rats using both biochemical and morphological techniques, and the results were compared with observations on the whole forebrain or on the cerebral cortex. The longitudinal growth, area and the volume of the hippocampus was severely reduced in thyroid deficiency. In the cerebral cortex the longitudinal growth and some of the parameters of transverse development were significantly decreased at the rostral but not at the caudal level. On rehabilitation from day 35 to 160 the longitudinal growth remained decreased in both the brain parts while the transverse growth was restored to normal in the cerebral cortex but not in the hippocampus. In the normal hippocampus about 60% of the cells were formed during the first 3 postnatal weeks. This developmental increase was significantly depressed in hypothyroid rats; the final deficit in cell number was about 13%. The rate of cell acquisition was calculated from the slopes of the logistic curves fitted to the data of DNA content. At the age of maximal cell acquisition (at day 2-3) the daily deposition was 0.44x106 cells in controls and 0.34x106 cells in the hypothyroid rats. In controls the concentration of DNA decreased in the hippocampus during maturation. Thyroid deficiency did not influence this developmental trend. In contrast, a severe reduction was observed in the cellular composition of RNA and protein.

Animals↗
PubMed1978

Effect of undernutrition on the regional development of transmitter enzymes: glutamate decarboxylase and choline acetyltransferase.

The effect of undernutrition on the activity of glutamate decarboxylase (GAD) and choline acetyltransferase (ChAc) (markers for the GABA-ergic and the cholinergic transmitter system, respectively) was studied in various parts of the rat brain at the age of 10, 15 and 21 days, and at day 54 following 33 days of rehabilitation. The brain regions investigated were the olfactory bulbs, cerebellum, pons-medulla, hypothalamus, colliculi, cerebral cortex hippocampus and the residual brain. Undernutrition resulted in a marked retardation of the developmental rise of the activities of both enzymes, expressed in terms of either total brain part or unit weight or protein. The effect diminished with age even during the period of nutritional deprivation. In most brain regions the enzyme activities were restored to normal after rehabilitation. In the cerebral cortex the total activity of both enzymes was persistently reduced, although the concentration of GAD exceeded the control levels. A negative correlation was manifested between the activities of GAD and ChAc in the different brain parts (except the cerebellum) during development. The correlation became significant by day 21 in the controls, but only after postweaning rehabilitation of the undernourished rats. The results showed therefore that undernutrition caused a reversible retardation in the development of these two transmitter enzymes, and they suggested that even the balance of the GABA-ergic and cholinergic systems throughout the brain can be restored to normal by rehabilitation.

Animals↗
PubMed1977

Effect of undernutrition on cell generation in the adult rat brain.

Cell proliferation and cell death in the lateral ventricular subependymal layer were studied in acutely food-deprived and chronically undernourished 6-week-old rats. The length of the cell cycle was increased by 40-75%, while the DNA synthesis phase of the cycle was prolonged by 70-85%. The rate of cell acquisition was reduced to approximately half the control level, and the proportion of degenerating cells was significantly increased. The response to undernutrition of proliferating cells in the subependymal layer of adult rats differs from that in animals in the first two weeks of life, and resembles that seen in other tissues.

Animals↗
PubMed1977

Effect of reserpine on cell proliferation in the developing rat bran: a biochemical study.

Reserpine, a well-known CNS depressant which depletes central monoamine stores, was found to produce in the brains of 11-day-old rats a severe depression in cell proliferation in terms of the rate of [3H]thymidine incorporation into DNA. The effect was studied in detail 12 h after ther administration of the drug (2.5 mg/kg, s.c.) when the rate of in vivo DNA synthesis in the forebrain was about one-third of control: the decrease was less marked in the cerebellum (rate about two-thirds of control). It was possible to exclude side effects of the drug, such as restricted food intake, hypothermia and an elevation of the level of blood corticosteroids being responsible for the reduction of [3H]thymidine incorporation into DNA. Kinetic studies showed that reserpine had no marked effect on the entry of [3H]thymidine from blood to brain, but it caused some retardation in the rate of [3H]thymidine conversion into [3H]thymidine nucleotides. Nevertheless, the severe depression of DNA labelling was evident even after correcting the values on the basis of [3H]thymidine nucleotide concentrations. In contrast to these effects, thymidine kinase activity was normal in the brain of reserpine-treated animals.

Animals↗
PubMed1977

Effect of reserpine on cell proliferation in the developing rat brain: a quantivative histological study.

Rats aged 11 days were injected with reserpine (2.5 mg/kg body wt.) and the rate of [3H]thymidine incorporation into brain DNA was followed over a period of 36h. In the forebrain this was significantly depressed by 2h, and it reached a nadir of about 30% of the control level at 4h, at which it remained for another 26h. A partial recovery occurred by 36h. The effect was less pronounced in the cerebellum. On the basis of this information brains of rats were examined histologically and by autoradiography between 7 and 36 h after reserpine to obtain estimates of cell cycle parameters and of rates of cell proliferation and cell loss. In the forebrain lateral ventricular subependymal layer the labelling index was markedly reduced in comparison withe controls. Cell cycle time was prolonged by 50% and turnover time increased by 60%. In the cerebellar external granular layer, the mitotic index was reduced and increased numbers of degenerate postmitotic nuclei were found, notably in the latter part of the experimental period. These effects are potentially of functional and clinical significance.

Animals↗