Perinatal hypoxia induces a long-lasting increase in unstimulated gaba release in rat brain cortex and hippocampus. The protective effect of pyruvate.
Hypoxia and seizures early in life can cause multiple neurological deficits and even chronic epilepsy. Here, we report the data obtained in rats exposed to hypoxia and seizures at age 10-12 postnatal days and taken in experiments 8-9 weeks after hypoxia treatment. A level of the extracellular GABA and the initial velocity of GABA uptake were measured in the brain cortex, hippocampus and thalamus using isolated nerve terminals (synaptosomes). It has been revealed that the extracellular [(3)H]GABA level maintained by cortical and hippocampal synaptosomes in standard conditions (with glucose as an energy substrate) was significantly higher in adult rats exposed to hypoxia/seizures at P10-12 than in the control ones, and, moreover, became unstable with tendency to increase. Pyruvate as a single energy substrate was shown to be a highly effective for lowering and stabilizing the extracellular [(3)H]GABA level. This effect of pyruvate was tightly correlated with increase in GABA uptake and GATs affinity to GABA. Thalamus was insensible to the action of perinatal hypoxia/seizures, and thalamic GATs, in contrast to cortical and hippocampal ones, had a lower affinity to GABA (the apparent Km is 39.2±3.1 μM GABA vs 8.9±1.8 μM GABA in the hippocampus). A selective vulnerability of brain regions to hypoxia is suggested to be attributed to distinct terms of their maturation at the postnatal period. Thus, perinatal hypoxia/seizures evoke a long-lasting increase in the extracellular GABA level that could be attenuated by pyruvate treatment. This effect of pyruvate is likely due to a significant increase in GATs-mediated GABA uptake and modulation of GATs kinetic properties.
Department of Neurochemistry, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine.
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N
Pozdnyakova
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Yatsenko
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Parkhomenko
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Himmelreich
D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D019289:Pyruvic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000209:etiology / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid; D019289:Pyruvic Acid