title: Diazepam treatment blocks the elevation of hippocampal activity and the accelerated proliferation of hippocampal neural stem cells after focal cerebral ischemia in mice.
abstract: Hippocampal neurogenesis is accelerated during the elevation of hippocampal neural activities under both physiological and pathophysiological conditions. One of these conditions, middle cerebral artery occlusion (MCAO), induces both the hyperactivities of hippocampal network and the elevation of neural stem cell (NSC) proliferation. However, the causal relationship between the elevated activity and the elevation of NSC proliferation is still unclear. In this study, to block the elevation of hippocampal activity after MCAO in mice, we utilized a typical γ-aminobutyric acid type A (GABAA ) receptor active modulator, diazepam. With MCAO mice treated with diazepam, we observed complete disappearance of the elevation of hippocampal activity. Additionally, the diazepam treatment blocked the elevation of NSC proliferation after MCAO. From this result, it is speculated that the increased NSC proliferation is blocked by the suppression of elevated neural activity. However, diazepam might have effects other than the suppression of hippocampal activity, so we performed additional experiment and found that diazepam did not affect the number of bromodeoxyuridine-positive cells under the normal condition, whereas the GABA agonist pentobarbital stimulated NSC/neural progenitor cell proliferation and differentiation. Next, we evaluated the expression of the diazepam-binding inhibitor (DBI) protein and found that the cells expressed DBI in soma and on the surface of cell membrane. From these observations, we can propose that diazepam blocks the elevation of hippocampal activity and also NSC proliferation after MCAO.
authors: Department of Integrated Biosciences, The University of Tokyo, Kashiwa, Chiba, Japan.
authors: Rokuya
authors: R
authors: Nochi
authors: Jun
authors: J
authors: Kaneko
authors: Natsumi
authors: N
authors: Okada
authors: Yasushi
authors: Y
authors: Terazono
authors: Ayumu
authors: A
authors: Matani
authors: Tatsuhiro
authors: T
authors: Hisatsune
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology*; D004195:Disease Models, Animal; D004594:Electrophysiology; D018757:GABA Modulators / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000187:drug effects*
chemical_list: D018757:GABA Modulators; D003975:Diazepam
keywords: diazepam; hippocampus; ischemia; neural activity; neural stem cell