| 研究実績の概要 |
In this research project we aim to identify brain regions and signaling pathways underlying cannabinoid-induced seizures. As we showed in our previous research natural and synthetic cannabinoids induce epileptic seizures in mice (Malyshevskaya et al., 2017), however their appearance is different form classic epileptic seizure. The difference of severity, seizure duration time, and the fact that these seizures are prevented by CB1R-blocker also suggest a completely distinct mechanisms from classical epileptic seizure models. Therefore using CB1RKO mice we confirmed their resistance to the cannabinoid convulsive effects. We also discovered certain brain regions are activated upon synthetic cannabinoid JWH-018 administration. With in-situ hybridization (ISH) method we found that c-fos (immediate early gene) mRNA expression is increased in the hypothalamic paraventricular (PVN) and supraoptic (SO) nuclei, 1 hour after cannabinoid administration, which were not activated in control mice. To verify brain regions involved in cannabinoid convulsive effects we used optogenetic activation of SO nuclei. Bilateral photostimulation of SO nuclei alone did not induce electrographic seizures. Therefore we are testing the possibility of importance of both PVN and SO nuclei in seizure induction process which requires mutual photostimulation. The experiment with complex AAV injection and photostimulation is ongoing.
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