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Biomedical subjects

P Mandel

Publications and source records attributed to P Mandel.

At least 397 records · Page 22Linked to original sources

Effects of hippocampal electrical stimulation on longterm memory and on cholinergic mechanisms in three inbred strains of mice.

Two sets of experiments have been carried out in an attempt to determine the role of hippocampal cholinergic mechanisms in a long-term memory storage. Three inbred strains of mice were presented with two different learning tasks in order to estimate their long-term retention abilities as well as changes in this ability after a post-trial hippocampal stimulation. In parallel experiments the enzymes involved in acetylcholine metabolism were studied under different experimental conditions. Our results indicate: (a) The capacity for long-term memory of the BALB/c line is much greater than that of either the C57BL/6 or C57BR strain. (b) Hippocampal post-trial electrical stimulation leads to an improvement of this capacity in the BALB/c strain. This phenomenon is less pronounced in C57BL/6 and non-existent in C57BR mice. (c) Choline acetyltransferase activity in the hippocampus is significantly higher in BALB/c than in the other two strains. In BALB/c this enzyme activity is greatly changed by the post-trial stimulation whereas in the C57BL/L strain only a slight variation of enzyme activity is observed. No modification occurs in C57BR. The results suggest that the more active acetylcholine synthesizing enzyme in the hippocampus of BALB/c may be related to a greater acetylcholine availability, thus favoring the establishment of a long-term memory, perhaps by releasing greater amounts of acetylcholine in the hippocampus immmediately after the learning session. The electrical stimulation of the hippocampus acts to magnify or accelerate this phenomenon. It is suggested that the efficiency of the stimulation would be related to the genetically determined higher cholinergic activity of the hippocampus.

Acetylcholine↗

The association of the sulphogalactosylglycerolipid of rat brain with myelination.

The sulphogalactosylglycerolipid of rat brain is closely associated with the process of myelination, as demonstrated by the following observations. 1. The lipid is barely detectable in rat brain before 10 days of age, accumulates rapidly between age 10 and 25 days, and remains relatively constant in amount (between 0.3 and 0.4mumol per brain) thereafter into adult life. 2. The activity of adenosine 3'-phosphate 5'-sulphatophosphate-galactosyldiacylglycerol sulphotransferase is almost absent before 10 days of age, attains a maximum at age 20 days, and slowly decreases thereafter with increasing age. This developmental pattern correlates well with that of other myelin-specific metabolites. 3. Both the concentration of the sulphogalactosylglycerolipid and the activity of sulphotransferase are greatly decreased in the non-myelinating jimpy mouse. 4. The myelin fraction of rat brain contains most of the sulphogalactosylglycerolipid. The lipid occurs in a diacyl and an alkylacyl form. Determinations of the relative amount of each type in brain showed about a 1:1 mixture in both 21-day-old and adult rats. Rats injected with H(2) (35)SO(4) at 20 days of age lost (35)S from the diacyl form at a higher rate than from the alkylacyl compound over a 21-day period. These data suggest that the diacyl form has a higher turnover than the alkylacyl derivative. The percentage of the total sulpholipid content of brain contributed by the sulphogalactosylglycerolipid is 16% in 21-day-old rats and 8.4% in adult rats.

Age Factors↗

Immunohistochemical studies of Wolfgram proteins in central nervous system of neurological mutant mice.

Immunohistochemical localization of Wolfgram proteins has been studied by the indirect immunoperoxidase technique with Wolfgram protein W1 antibodies in the nervous system of myelin deficient mutant mice: Jimpy, MSD and Quaking. In all these mutants, the myelinated fibers and the oligodendroglial cells (few in number) in the corpus callosum and the white matter of the cerebellum folium show a positive reaction to protein W1. These observations are in accordance with the immunological studies showing that the two major Wolfgram proteins, W1 and W2, of mutant mice have immunological similarities with that of the controls.

Animals↗

Purification and some properties of arylsulphatases A and B from rabbit kidney cortex.

Arylsulphatases A and B (EC 3.1.6.1) of rabbit kidney cortex were purified 5250- and 7720-fold respectively by a multiple-column-chromatography method. The specific activity toward 4-nitrocatechol sulphate was 42mumol/min per mg for arylsulphatase A and 62 mumol/min per mg for arylsulphatase B. Each enzyme migrated as a single band on polyacrylamide-gel electrophoresis, and the enzyme activity corresponded to the band of protein on the gel. The rate of hydrolysis of ascorbic acid 2-sulphate by arylsulphatase A was three times that for cerebroside 3-sulphate. Arylsulphatase B hydrolysed UDP-N--acetylgalactosamine 4-sulphate and glucosamine 4,6-disulphate, but not galactosamine 6-sulphate.

Animals↗

Gangliosides of active and inactive neuroblastoma clones.

It is possible to divide neuroblastoma cells into clones able to synthesize neurotransmitters (active clones) or not (inactive clones). The analysis of gangliosides of active and inactive clones shows that their total lipid sialic acids is markedly lower than that of neuron-enriched fractions prepared from brain. The ganglioside pattern of the cultured cells also differs notably from those obtained with neuronal fractions from brain. The absence of tri- and tetrasialogangliosides and the presence of appreciable amounts of the simplest monosialogangliosides are particularly noticeable in the neuroblastoma. Morphological differentiation obtained by serum deprivation, dibutyryl cyclic AMP or bromodeoxyuridine does not restore a true neuronal pattern. Gangliosides could not therefore be used as a marker of neuronal differentiation in this type of cell. No correlations can be found between the ganglioside pattern and the ability of cells to synthesize neurotransmitters.

Bromodeoxyuridine↗

Preferential neurotoxicity of pentobarbital on nerve and glial cells in culture.

The effect of pentobarbital was studied in a mixed population of nerve and glial cells dissociated from brains of 7-day chick embryos and maintained in culture. Pentobarbital-Na was added in various concentrations ranging from 5 X 10(-5) M to 1 X 10(-3) M. The neuronal density was monitored by counting the neurons, neuronal identity was established by staining for Nissl Bodies and acetylcholinesterase. Over a culture period of 3 weeks, it was found that the barbiturate exerts a preferential dose-dependent cytotoxic effect on neurons.

Animals↗

[Effects of chloroiodoquine and lethal doses in various mouse strains].

Chloroiodoquine has been implied in numerous cases of myeloneuropathy in Japan, while in other countries although equally frequently used, only a few cases have been reported after treatment with this drug. Studies on the effect of chloroiodoquine in mice of various inbred strains or from crossings between sensitive and insensitive strains demonstrated a genetic predisposition of sensitivity to chloroiodoquine.

Animals↗

[Identification of catecholamines and serotonin in the notochords of chick embryos].

The neurotransmitter amines, norepinephrine, dopamine and serotonine have been isolated from Chick notochords. Cholinergic agents produce important modifications in the amount of these amines and of one of their metabolites. The results demonstrate the presence, at a very early stage of development, between the second and the third day of incubation, of biogenic amines and cholinergic receptors.

Animals↗

Neuroblasts-glia interaction in tissue culture as evidenced by the study of ectoenzymes. Ecto-ATPase activity of mouse neuroblastoma cells.

Ecto-ATPase and ecto-5'-nucleotidase activities of hamster astroblasts, clonal line NN, and mouse neuroblasts, clonal line Ml in coculture, have been studied. The originally low ecto-ATPase activity in both cell lines increased many fold when these cell lines were cocultured. An increase of ecto-ATPase activity was also found in coculture of neuroblastoma cells with chick fibroblasts. Neuroblastoma Ml cells were separated from coculture with hamster astroblasts after 7 days and 2 months. Reisolated M1 cell lines exhibited higher ecto-ATPase activity than the original M1 cell line. The M1 cell line separated after 2 months of coculture had higher ecto-ATPase activity than the M1 cell line separated after 7 days of coculture with hamster astroblasts. This higher ecto-ATPase activity continued for more than 20 replications after separation of the M1 cells from the glial cells.

Adenosine Triphosphatases↗

Nuclear, nucleolar repair, or turnover of DNA in adult rat brain.

Labeled thymidine administered to adult rats is incorporated at a low level into brain DNA as shown by biochemical and autoradiographic methods. This incorporation takes place in part into neuronal nuclei and nucleoli and also into glial nuclei. While incorporation into glial nuclei is interpreted to represent known glial cell proliferation, incorporation into neuronal nucleoli may be related to nucleolar DNA synthesis, which in turn is responsible for the regulation of nucleolar RNA synthesis. It could also be due to DNA repair synthesis. Assuming this latter phenomenon, our results suggest that nucleolar DNA is more sensitive than chromosomal DNA to ionizing radiations and other factors.

Animals↗

Free amino acid pool in the brain of mice homozygous for the gene "dilute lethal".

The neurologic mutant "dilute lethal" (dl) mice, which reveal several neurologic and biochemical disturbances similar to human phenylketonuria, were used to investigate some aspects of amino acid disorder. We have studied the free amino pool in the brain of "dl" mice and of their control littermates as well as phenylalanine and tyrosine levels in brain and liver as a function of age and after phenylalamine overload. The tyrosine level decreased in brain and liver of affected mice whereas the phenylalanine/tyrosine ratio increased as a function of age. The significantly higher phenylalanine level and phenylalanine/tyrosine ratio in the liver of 20-day-old "dl" mice suggest a lower liver phenylalanine hydroxylase activity. After phenylalanine overload, the impairment of phenylalanine metabolism is predominant in the brain of "dl" mice, suggesting a disturbance in phenylalanine hydroxylation. A decrease in the level of several amino acids occurs in the brains of "dl" mice without or after phenylalanine overload; these facts might correspond to a disturbance in the transfer of amino acids to the brain and may lead to impairment in protein synthesis.

Amino Acids↗