ИСТИНА

A number of inborn and acquired neuropathologies are associated with impaired function of the mitochondrial 2-oxoglutarate dehydrogenase multienzyme complex (OGDHC). To relate the OGDHC function and overall physiology, the "open field" test and ECG of animals subjected to the OGDHC inhibitor succinyl phosphonate, SP (5 mg/kg) or acute hypobaric hypoxia were performed, followed by the assays of the brain OGDHC and excitatory neurotransmitter glutamate. We also used the two physiological states of animals (non-pregnant and pregnant rats) to follow their potentially different reactivity to the OGDHC modulation. Effects of toxical stress on all investigated parameters were more expressed. So, SP but not hypoxia caused a decrease in locomotor and exploratory activities in non-pregnant rats (the reduced linear locomotion and rearing) and an increase of anxiety level (the increased number of grooming and grooming latency) along with opposite effect in pregnant ones. SP also changed regulation of cardiovascular system: increased contribution of the parasympathetic regulation in non-pregnant rats (increase in relaxation index -RMSSD and a decrease in stress index -SI), with the opposite effect in the pregnant ones SP induced interdependent changes in the OGDHC activity and glutamate levels in cortex: both glutamate and the OGDHC activity elevated in pregnant rats, but decreased in non-pregnant. The opposite action on the OGDHC activity correlated with the initial OGDHC level. That is, the up-regulation was observed only when the initial OGDHC level was low. Thus, both animal groups showed the changes in the behavioral and ECG parameters according to the changes in the cortex OGDHC activity and glutamate levels in response to toxical stress. These findings establish physiological importance of the OGDHC regulation at the level of behavioral activity and ECG parameters, which may be due to the impact of the OGDHC function on the production of the neurotransmitter glutamate.