Toshiaki Kume

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Multiple lines of evidence, from molecular and cellular to epidemiological, have implicated nicotinic transmission in the pathogenesis of Alzheimer's disease (AD). Here we show the signal transduction mechanism involved in nicotinic receptor-mediated protection against beta-amyloid-enhanced glutamate neurotoxicity. Nicotine-induced protection was suppressed(More)
Localization of the mRNAs for fractalkine, a CX3C chemokine, and for its receptor CX3CR1 was investigated in the rat brain. In situ hybridization study revealed that fractalkine mRNA was dominantly expressed in neuronal cells particularly in the olfactory bulb, cerebral cortex, hippocampus, caudate putamen and nucleus accumbens. In vitro study using(More)
beta-Amyloid (A beta), a major constituent of senile plaques in Alzheimer's disease (AD), is thought to contribute to the neurodegeneration. We examined the effects of nicotinic receptor agonists on A beta cytotoxicity in cultured rat cortical neurons. The number of viable neurons decreased significantly when cultures were exposed to synthetic A beta(More)
Increasing lines of evidence show that resveratrol, a polyphenol compound contained in several dietary products, exhibits cytoprotective actions. Notably, resveratrol activates sirtuin family of NAD-dependent histone deacetylases implicated in regulation of various cellular processes including gene transcription, DNA repair and apoptosis. Here we examined(More)
N-methyl-D-aspartate (NMDA) receptors, whose activation requires glycine site stimulation, play crucial roles in various physiological and pathological conditions in the brain. We investigated the regulatory roles of potential endogenous glycine site agonists, glycine and d-serine, in excitotoxic and ischemic cell death in the cerebral cortex. Cytotoxicity(More)
Donepezil is a potent and selective acetylcholinesterase (AChE) inhibitor developed for the treatment of Alzheimer's disease. To elucidate whether donepezil shows neuroprotective action in addition to amelioration of cognitive deficits, we examined the effects of donepezil on glutamate-induced neurotoxicity using primary cultures of rat cortical neurons. A(More)
We examined the effects of nicotine on glutamate-induced cytotoxicity using primary cultures of rat cortical neurons. The cell viability decreased significantly when cultures were exposed to glutamate for 10 min and then incubated with glutamate-free medium for 1 h. The exposure of cultures to nicotine (10 microM) for 8-24 h prior to glutamate application(More)
A brief exposure to hydrogen peroxide (H2O2) induces severe deterioration of primary cultured neurons in vitro. We have investigated a link between the H2O2-induced neuronal death and Ca2+-permeable TRPM2 channels regulated by ADP-ribose (ADPR). In cultured cerebral cortical neurons from fetal rat, TRPM2 proteins were detected at cell bodies and neurite(More)
We investigated the effects of sigma receptor ligands on neuronal death induced by chemical ischemia using primary cultures of rat cerebral cortical neurons. The induction of chemical ischemia by sodium azide and 2-deoxy-D-glucose led to delayed neuronal death in a time- and concentration-dependent manner, as determined by trypan blue exclusion. The(More)
The effects of brain-derived neurotrophic factor (BDNF) on glutamate-induced cytotoxicity were examined using primary cultures of rat cortical neurons. BDNF induced TrkB tyrosine phosphorylation in rat cultured cortical neurons. The cell viability was significantly reduced when cultures were briefly exposed to glutamate and incubated with normal medium for(More)