@article{oai:kumadai.repo.nii.ac.jp:00021866,
 author = {香月, 博志 and 大川原, 賦 and 柴田, 治樹 and 久米, 利明 and 赤池, 昭紀 and 香月, 博志 and Katsuki, Hiroshi and Okawara, Mitsugu and Shibata, Haruki and 久米, 利明 and Kume, Toshiaki and 赤池, 昭紀 and Akaike, Akinori},
 issue = {5},
 journal = {Journal of Neurochemistry},
 month = {Jun},
 note = {application/pdf, 論文(Article), Activated microglia are considered to play important roles in degenerative processes of midbrain dopaminergic neurons. Here we examined mechanisms of neurotoxicity of thrombin, a protease known to trigger microglial activation, in organotypic midbrain slice cultures. Thrombin induced a progressive decline in the number of dopaminergic neurons, an increase in nitric oxide (NO) production, and whole tissue injury indicated by lactate dehydrogenase release and propidium iodide uptake. Microglia expressed inducible NO synthase (iNOS) in response to thrombin, and inhibition of iNOS rescued dopaminergic neurons without affecting whole tissue injury. Inhibitors of mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase (ERK), p38 MAPK and c-Jun N-terminal kinase (JNK) attenuated thrombin-induced iNOS induction and dopaminergic cell death. Whole tissue injury was also attenuated by inhibition of ERK and p38 MAPK. Moreover, depletion of resident microglia from midbrain slices abrogated thrombin-induced NO production and dopaminergic cell death, but did not inhibit tissue injury. Finally, antioxidative drugs prevented thrombin-induced dopaminergic cell death without affecting whole tissue injury. Hence, NO production resulting from MAPK-dependent microglial iNOS induction is a crucial event in thrombin-induced dopaminergic neurodegeneration, whereas damage of other midbrain cells is MAPK-dependent but is NO-independent., http://www.blackwellpublishing.com/jnc_enhanced/},
 pages = {1232--1242},
 title = {Nitric oxide-producing microglia mediate thrombin-induced degeneration of dopaminergic neurons in rat midbrain slice culture},
 volume = {97},
 year = {2006},
 yomi = {カツキ, ヒロシ and クメ, トシアキ and アカイケ, アキノリ}
}