Hyperexcitability of pyramidal neurons in field CA1 in hippocampal slices from rats evoked by episodes of hypoxia: the roles of GABAA and GABAB receptors.
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Biomedical subjects
Publications and source records attributed to O V Godukhin.
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Preconditioning of the cerebral cortex was induced in mice by repeated cortical spreading depression (CSD), and the major ionotropic glutamate (GluRs) and nicotinic acetylcholine receptor (nAChRs) subunits were compared by quantitative immunoblotting between sham- and preconditioned cortex, 24 h after treatment. A 30% reduction in alpha-amino-3-hydroxy-5-methyl-4-iso- xazolepropionate (AMPA) GluR1 and 2 subunit immunoreactivities was observed in the preconditioned cortex (p < 0.03), but there was no significant change in the NMDA receptor subunits, NR1, NR2A and NR2B. A 12-15-fold increase in alpha7 nAChR subunit expression following in vivo CSD (p < 0.001) was by far the most remarkable change associated with preconditioning. In contrast, the alpha4 nAChR subunit was not altered. These data point to the alpha7 nAChR as a potential new target for neuroprotection because preconditioning increases consistently the tolerance of the brain to acute insults such as ischaemia. These data complement recent studies implicating alpha7 nAChR overexpression in the amelioration of chronic neuropathologies, notably Alzheimer's disease (AD).
The purpose of this study was to ascertain whether or not spreading depression (CSD) propagates symmetrically along the anteroposterior axis of the cortex of mice, and to determine where CSD should be elicited to achieve a uniform exposure of the cortex to this phenomenon. Experiments were performed in halothane-anesthetized mice, with three different locations aligned 1.5 mm from the midline used for either KCl elicitation of CSD or the recording of its propagation. Our results demonstrated that, at least in the mouse cortex, CSD propagated much more effectively from posterior to anterior regions than in the opposite direction. This feature was due to a different efficacy of propagation in the two opposite directions, and not to a reduced susceptibility of occipital regions to CSD elicitation. Heterogeneous CSD propagation constitutes a potential pitfall for neurochemical studies of post-CSD changes in mice, as brain tissue samples collected for this purpose should be uniformly exposed to CSD. Occipital sites for CSD induction are clearly optimal for this purpose. If CSD propagation is confirmed to be more effective from posterior to anterior regions in other species, this may be relevant to the pathophysiology of classical migraine because the most frequent aura symptoms (i.e., visual disturbances) originate in the occipital cortex.
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Short-term repeated increases of extracellular K+ resulted in occurrence of a kindling-like phenomenon in local neuronal network of the CA1 region in hippocampal slices. The phenomenon well correlated with the ES potentiation. The role of various Ca2+ channels in this phenomenon is discussed.
Several putative neurotransmitters and metabolites were monitored simultaneously in the extracellular space of neostriatum, substantia nigra, and cortex and in subcutaneous tissue of the rat by in vivo microdialysis. Glutamate (Glu) and aspartate (Asp) were at submicromolar and gamma-aminobutyric acid (GABA) was at nanomolar concentrations in all brain regions. The highest concentration of dopamine (DA) was in the neostriatum. Dynorphin B (Dyn B) was in the picomolar range in all brain regions. Although no GABA, DA, or Dyn B could be detected in subcutaneous tissue, Glu and Asp levels were 5 and approximately 5 and approximately 0.4 microM, respectively. Lactate and pyruvate concentrations were approximately 200 and approximately 10 microM in all regions. The following criteria were applied to ascertain the neuronal origin of substances quantified by microdialysis: sensitivity to (a) K+ depolarization, (b) Na+ channel blockade, (c) removal of extracellular Ca2+, and (d) depletion of presynaptic vesicles by local administration of alpha-latrotoxin. DA, Dyn B, and GABA largely satisfied all these criteria. In contrast, Glu and Asp levels were not greatly affected by K+ depolarization and were increased by perfusing with tetrodotoxin or with Ca2+-free medium, arguing against a neuronal origin. However, Glu and Asp, as well as DA and GABA, levels were decreased under both basal and K+-depolarizing conditions by alpha-latrotoxin. Because the effect of K+ depolarization on Glu and Asp could be masked by reuptake into nerve terminals and glial cells, the reuptake blocker dihydrokainic acid (DHKA) or L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) was included in the microdialysis perfusion medium. The effect of K+ depolarization on Glu and Asp levels was increased by DHKA, but GABA levels were also affected. In contrast, PDC increased only Glu levels. It is concluded that there is pool of releasable Glu and Asp in the rat brain. However, extracellular levels of amino acids monitored by in vivo microdialysis reflect the balance between neuronal release and reuptake into surrounding nerve terminals and glial elements.
A purified preparation of endogenous RNA-dependent DNA-polymerase (reverse transcriptase) earlier identified in rat brain (Ivanov, V.A., Pakhotin, P.I., Bobkova, N.V., and Ilyin, Yu.V. parallel Dokl. RAN (1992). V. 323, P. 173-177) has been obtained. A comparative analysis of the enzyme and recombinant reverse transcriptase coded by the mobile genome element jockey earlier expressed in a heterological cell system (Ivanov V.V., Melnikov A.A., Siunov A.V., Fodor I.I., Ilyin, Yu.V. parallel EMBO J. (1991), V. 10, P. 2489-2495) has been carried out. Like retroviral RNA-dependent DNA-polymerases, these enzymes show preference for polyribonucleotides and can use poly(rCm) as template. Besides they are inhibited by SH-reagents and require bivalent cations (Mg2+ or Mn2+) and detergent and/or KCl as ionic strength carrier. The enzymes differ drastically from retrovirus reverse transcriptases by a number of catalytic properties (low optima of concentration of requisite cations and ionic strength, strong preference for Mn2+, highly efficiency in using poly(rCm), lack of associated RNase H activity) but exhibit a high degree of similarity among themselves with regard to the above properties. It is suggested that endogenous reverse transcriptase from rat brain is a product of expression of the mobile genome element of the LINE family.
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Sodium succinate has been studied for its influence on the efficiency of glutamate transmission in the Schaffer collateral synapses and duration of its potentiation state caused by high-frequency stimulation in surviving hippocampal slices. It is shown that administration of sodium succinate (50 mg/kg i. p.) to rats 30 min prior to decapitation stabilizes glutamate transmission in field CA1 of the rat hippocampal slices and increases duration of its potentiation state.
The effect of methionine-enkephalin (Met-Enk) on responses of rat brain neostriatum neurones to microiontophoretic application of glutamate was studied in experiments with extracellular recording of spike activity. Met-Enk administered by microiontophoresis was shown to depress the glutamate-induced responses. In parallel experiments with synaptic membranes isolated from the striatum it was shown that Met-Enk reduces specific binding of glutamate. Analysis of binding curves suggests that the reduced [3H]glutamate binding in the rat striatum membranes was due to decreased binding sites, whereas binding affinity was not changed. The data obtained show that the depressive effect of Met-Enk may be due to the inhibitory influence of the peptide on glutamate binding to its postsynaptic receptors.
The influence of microionophoretically applied dopamine and dibutyril cAMP on the background and glutamate-evoked spike activity of neostriatum neurons was studied in acute experiments on rats immobilized by d-tubocurarine. The mean rate, stationarity, interspike interval histograms and autocorrelation functions for extracellularly recorded spike activity were measured. It was shown that dibutyril cAMP imitated the inhibiting dopamine effect on the background and glutamate-evoked spike activity of neostriatum neurons rather than the stimulating effect.