Biomedical subjects
Publications and source records attributed to P Mandel.
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The acquisition of ultrastructural and neurochemical properties was studied during the development of neurones from 8-day-old chick embryo cerebral hemispheres, cultivated on polylysine-coated surfaces. The first contacts suggestive of synaptic profiles were observed after 3 days of culture. From the 6th day, junctions with significant thickening of the postsynaptic element and many presynaptic vesicles could be seen. Synaptic endings contained predominantly dense-cored vesicles. These cultured neurones acquired dopaminergic properties during their development: (1) 95% of the cells exhibited glyoxylic acid-induced fluorescence; (2) tyrosine hydroxylase and dopa decarboxylase activities were present and increased with time in culture, but dopamine-beta-hydroxylase activity was undetectable. Choline acetyltransferase activity remained at a very low level at all stages of culture. It is suggested that when cultured in the total absence of glial cells, the neurones of embryonic chick cerebral hemispheres give no evidence of cholinergic mechanisms, but display a number of dopaminergic characteristics.
The effect of acute and chronic ethanol administration on rat brain superoxide dismutase (SOD) activity was studied. Intraperitoneal injections of ethanol led to an inhibition of SOD activity. When ethanol was fed as the sole fluid, the SOD activity decreased progressively, reaching a plateau after 6 weeks of treatment. Withdrawal of ethanol produced a recovery of control values within 48 hr. SOD activity was also decreased in rats born from ethanol-drinking mothers. Inhibition of SOD activity by ethanol may allow an accumulation of cytotoxic O2 - radicals; this may account for some nervous system disorders during alcohol intoxication.
Repeated audiogenic seizures (4 times a day for 14 days), in genetically selected sensitive mice, induce a significant decrease in GABA level in the following brain areas: nucleus caudatus, posterior colliculus, occipital and frontal cortex, cerebellum, substantia nigra, hippocampus, amygdala, and temporal cortex. No variations were observed in olfactory bulbs, pons medulla, hypothalamus, thalamus, or cochlear area.
Two different preparations isolated from beef cerebrum have been used to compare the polyadenosine diphosphate ribose (polyADPR) polymerase activities in neuronal and glial nuclei: (1) nuclear suspensions (with or without DNase I treatment), and (2) 1 M NaCl nuclear extracts (soluble enzyme). The DNAse I treatment of nuclei and the solubilization of polyADPR polymerase by 1 M NaCl enhances the polyADPR polymerase activity. The polyADPR polymerase activity is similar in neuronal and glial nuclear suspensions, while the neuronal soluble enzyme activity is significantly higher than that of the glial soluble enzyme. Evidence is presented that the difference in soluble enzyme activities is not due to the effects of DNA or degrading enzymes. Some activating factor(s) seem to be present in neuronal soluble extracts, while both inhibiting and activating factor(s) seem to be present in glial soluble extracts.
Cysteine sulfinate transaminase catalyzes the conversion of cysteine sulfinate and alpha-ketoglutarate to beta-sulfonyl pyruvate and glutamate and is present in high concentration in neuronal tissue. During development, levels of cysteine sulfinate transaminase in whole rat brain homogenate increase twofold between days 10 and 21. At maturity, high levels of the enzyme are present in the synaptosomal fraction. The highest level of enzyme activity was in the hypothalamus, approximately three- to fourfold greater than any other region examined. These data suggest that cysteine sulfinate transaminase may have an important role in the metabolism of neurotransmitters and their precursors.
Although their body weights were decreased by about 77% and their brain weights by about 30%, high-affinity [3H] muscimol binding to a cerebral membrane fraction was not altered in hereditary pituitary dwarf mice. Marked changes in the level of pituitary growth-associated hormones do not appear to be associated with a change in cerebral GABA-receptors.
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Explore the source record for details and available documents.
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The effects of drugs that antagonize or potentiate the action of brain gamma-aminobutyric acid (GABA) on shock-induced aggressive behavior in mice were investigated. In previous studies it has been shown that in C57 BL/6 strain shock-induced aggressive behavior is absent up to the 10th week of age and rises to the highest intensity after the 20th week, while at the same ages aggressive responses are lowest or absent in DBA/2 strain. GABA antagonist, picrotoxin and glutamic acid decarboxylase (GAD) inhibitor, D, L-allylglycine induced aggressive responses in non-aggressive 10 week old C57 BL/6 and 20 week old DBA/2 mice. GABA agonist muscimol hydrobromide, and GABA-T inhibitor sodium n-dipropylacetate inhibited aggressive responses in 20 week old C57 BL/6 mice. These effects were not related to changes in shock sensitivity and motor activity. The results strongly suggest that the GABAergic system is involved in the control of shock-induced aggressive behavior in mice and that this control is related to developmental and genetic factors.
Bovine rhodopsin from retinal rod photoreceptors, a protein of 39,000 molecular weight, was cleaved by BNPS-Skatole at the level of tryptophanyl bonds. This hydrolysis yields five fragments S1, S2, S3, S4 and S5 (molecular weights: 35,000, 28,000, 19,500, and 15,500 and 12,000, respectively) and four peptides. Large fragments were purified by polyacrylamide gel electrophoresis in SDS. S2, S3 and S4 contain the glycanes of native rhodopsin and their N-termini are blocked. S5 has the same C-terminal extremity as rhodopsin and contains the phosphorylated site. Phosphate groups are incorporated in this fragment on serines and threonines.
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Rat brain contains two major NADPH-linked aldehyde reductases that can reduce succinate semialdehyde to 4-hydroxybutyrate. One of these enzymes appears to be fairly specific for succinate semialdehyde and is not significantly inhibited by classic aldehyde reductase inhibitors such as barbiturates. The other enzyme can reduce several aromatic aldehydes and is strongly inhibited by barbiturates and branched-chain fatty acids. Using one such inhibitor, it was possible to distinguish between and measure the two enzyme activities separately in various rat brain regions and in subcellular fractions. Both enzymes are mainly cytoplasmic but there is some activity in the synaptosomal fraction. The activity of the specific succinic semialdehyde reductase is highest in the cerebellum, where it represents 21% of the total activity, and lowest in the cortex, where it represents about 11% of the total activity.
Primary cultures of neurons and glial cells (astroblasts) prepared from brains of 8-day-old and 15-day-old chick embryos, respectively, were grown for periods between 3 and 19 days. Specific activity of lactate dehydrogenase (LDH) increased in both types of cultures as a function of time and was always significantly higher in glial cells than in neurons. Glial cell extracts were found to contain predominantly the anaerobic isoenzymatic form of LDH (LDH-M4), and this pattern did not change over a period of 19 days. Cultured neurons contained predominantly the aerobic isoenzymatic form LDH-H4, and there was a progressive appearance of all other isoenzymes over an 8-day period. These results support the hypothesis of a different energy metabolism in neurons and glia.
The uptake of calcium was examined in primary cultures of pure neurons and of glial cells from dissociated hemispheres of chick embryo brain. Neuronal cultures took up calcium at a rate of 2.0 nmol per min per mg cell protein at medium concentrations of 1.2 mM-Ca2+ and 5.4 mM-K+. The rate of calcium entry into neurons was increased 2.7-fold by elevating medium potassium to 60 mM. The effect of high external potassium was to increase the Vmax value for calcium transport from 5.5 to 13 nmol per min per mg; the Michaelis constant for calcium, 1.2 mM, was unchanged. The potassium-dependent component of calcium entry into the neuronal cultures was eliminated by addition of 0.1 mM-D-600 (a verapamil derivative) or by 1 mM-CoCl2, but 0.5 microM-tetrodotoxin had no significant effect. When choline replaced potassium in uptake medium no change in calcium transport was detected in neurons, nor was the entry of calcium increased when choline replaced sodium. Glial cultures took up calcium at 20% of the basal rate for neuronal cultures on a weight-of-protein basis. Uptake was not increased by potassium; during depolarization by potassium the calcium transport activity of glia was less than 10% that of neurons. It was concluded that cultured neurons contain a depolarization-sensitive, calcium-specific channel. A similar calcium transport activity was not detected in cultured glial cells.
UDP-galactose:ceramide galactosyltransferase (CGalT, EC 2.4.1.45) and UDP-glucose:ceramide glucosyltransferase (CGlcT, EC 2.4.1.80) were determined in the glial cell lines G26-20, G26-24, C6, and C6TK-. The enzymatic assay for CGalT in cultured glial cells was complicated by a rapid conversion of UDP-galactose to UDP-glucose, due to the elevated UDP-galactose-4'-epimerase activity in certain glial cell clones. It seems that mechanisms regulating UDP-galactose-4'-epimerase activity and levels of UDP sugars in the glial cell lines differ from those in brain tissue. Compared with the maximum activity of CGalT in the myelinating rat brain, the enzyme activities in the oligodendroglioma clonal cell lines G26-20 and G26-24 were 16-30 times lower. On the other hand, CGalT levels in G26-20 and G26-24 cells were comparable to the values found in young rat brain before myelination starts. No CGalT activity could be detected in C6 or C6TK- cells by the method used in this study, whereas CGlcT activity was found in all glial cell lines tested and its levels were close to the values observed in the young rat brain.