The physiological role of the lipid mediator on the synaptic plasticity in the central nervous system

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cPLA2 was used as the substantial lipid mediator which has been known abnormally expressed in the postmortem brain of the schizophrenic patients to investigate the physiological role of cPLA2 in the central nervous system in terms of the relation with the pathogenesis of schizophrenia. As the first experiment, we studied the physiological role of cPLA2 by using cPLA2 gene-deficient mouse. The knockout mice delivered as much number of pups as the wild-type mice. They revealed no particular abnormal appearance and behaviors as their phenotypes. The hippocampi were removed form the brain of four weeks old mice then slice samples were prepared. The electrophysiological recordings were obtained from the CA1 area then analyzed. The synaptic responses of filed EPSPs and EPSPs showed no particular abnormality by a single and multiple stimulation. The amplitude of LTP was not significantly different from wild-type mice, however, long-term depression induced by the application of low-frequency s … More tumuli was almost totally blocked in the knockout mice. As the second set of experiment, we examined the effect of arachidonic cascade which is existed as the downstream of cPLA2 on the induction of LTD. The application of 5-HETE in the postsynaptic cell through the patch clamp glass electrode did not recovered LTD induction, however, the application of 12-HPETE diffused into the postsynaptic cell recovered LTD induction. We concluded that the activity of 12-HPETE is required for the induction of LTD in the mouse hippocampal neurons. We investigated the effect of stress on the rat brain function. The restrain and force swimming stress were applied to the rat and electrophysiological properties and behavior tests were conducted. We found that LTP induction in the hippocampal pyramidal neurons was almost totally suppressed at one week after stress application, however, LTD induction was not affected. We also found that spatial learning was distorted and acoustic startle reflex was facilitated. Interestingly, this facilitation was inhibited in the presence of an antagonist of glucocorticoid receptor (GR1), suggesting that the effect of stress was at least partially through GR1 activation. We further need to investigate the relation of the activity between GR1 and lipid mediators. Less