Mamoru Shibata 교수

Intracellular accumulation of mutant Huntingtin with expanded polyglutamine provides a context-dependent cytotoxicity critical for the pathogenesis of Huntington disease (Everett, C. M., and Wood, N. W. (2004) Brain 127, 2385-2405). Here we demonstrate that the accumulation of mutant Huntingtin is highly sensitive to the expression of beclin 1, a gene essential for autophagy. Moreover, we show that the accumulated mutant Huntingtin recruits Beclin 1 and impairs the Beclin 1-mediated long lived p

Although oligodendrocytes (OLGs) are thought to be vulnerable to hypoxia and ischemia, little is known about the detailed mechanism by which these insults induce OLG death. From the clinical viewpoint, it is imperative to protect OLGs as well as neurons against ischemic injury (stroke), because they are the only myelin-forming cells of the central nervous system. Using the Cre/loxP system, we have established a transgenic mouse line that selectively expresses p35, a broad-spectrum caspase inhibi

Microglia play a pivotal role in innate immunity in the brain. During development, they mature from myeloerythroid progenitor cells in the yolk sac and colonize the brain to establish a resident population of tissue macrophages. In the postnatal brain, they exert phagocytosis and induce inflammatory response against invading pathogens. Microglia also act as guardians of brain homeostasis by surveying the microenvironment using motile processes. Cortical spreading depression (CSD) is a slowly pro

Single episodes of cortical spreading depression (CSD) are believed to cause typical migraine aura, whereas clusters of spreading depolarizations have been observed in cerebral ischemia and subarachnoid hemorrhage. We recently demonstrated that the release of high-mobility group box 1 (HMGB1) from cortical neurons after CSD in a rodent model is dependent on the number of CSD episodes, such that only multiple CSD episodes can induce significant HMGB1 release. Here, we report that only multiple CS

Background Recent genome-wide association studies have identified transient receptor potential M8 ( TRPM8) as a migraine susceptibility gene. TRPM8 is a nonselective cation channel that mediates cool perception. However, its precise role in migraine pathophysiology is elusive. Transient receptor potential V1 (TRPV1) is a nonselective cation channel activated by noxious heat. Both TRPM8 and TRPV1 are expressed in trigeminal ganglion (TG) neurons. Methods We investigated the functional roles of TR

We investigated the effect of nitric oxide (NO) on N-methyl-D-aspartate (NMDA)-induced changes in levels of dopamine (DA) and its metabolite in the striatum using in vivo microdialysis. Local administration of 1mM NMDA into the striatum significantly augmented DA release in the striatum. Simultaneous administration of -5mM N(G)-nitro-L-arginine methyl ester (-NAME), a NO synthase inhibitor, into the striatum significantly potentiated NMDA-induced DA release. This effect of L-NAME was completely

BH3-only proteins are a subfamily of proapoptotic Bcl-2 proteins that act upstream of the mitochondrially mediated cell death pathway, and their association with the pathogenesis of brain ischemia remains largely unknown. The authors explored the temporal profiles of the expression levels and subcellular localization of BH3-only proteins in permanent middle cerebral artery occlusion (MCAO) by Western blot analysis. They observed an increased mitochondrial distribution of Bim at 3 to 6 hours of M

We explored the expression of Smac/DIABLO, a newly identified mitochondrial apoptogenic molecule, and X-linked inhibitor of apoptosis protein (XIAP) in the brain subjected to ischemia/reperfusion. Transient focal ischemia was produced for 1 hour in mice. We observed only a negligible amount of Smac/DIABLO in both mitochondria and cytosol in the normal state. The mitochondrial expression level of Smac/DIABLO increased after 2-11 h reperfusion. There was increased Smac/DIABLO expression in the cyt

Although visual snow syndrome seems to be a heterogenous condition, our observations indicate that abnormal visual processing within the ventral visual stream may play a role in the pathogenesis of this condition.

ClinicalTrials.gov, NCT02959177 (registered November 7, 2016).