＜シンポジウム03―1＞脱髄性疾患におけるグリア間およびグリア・ニューロン間相互作用の破綻
神経科学から見た脱髄性疾患における免疫細胞・グリア・ニューロン間相互作用の異常
水野 哲也
国立大学法人名古屋大学環境医学研究所免疫系分野〔〒464―8601 名古屋市千種区不老町〕
Microglia play a crucial role in the development of inflammatory demyelinating lesions in multiple sclerosis (MS). Microglia act on inflammatory lymphocytes as antigen presenting cells, and produce inflammatory cytokines, glutamate, and reactive oxygen species (ROS). Neurodegeneration, which is observed in the demyelinating lesions, affects the prognosis in MS. Neuritic beading, focal bead-like swellings of the dendrites and axons, is a neuropathological sign in the early phase of neurodegeneration in MS. Microglia-derived glutamate and ROS initiate beading formation. Microglia can exert neuroprotective effect by deprivation of dead cells and induction of neurotrophic factors, anti-inflammatory cytokines, and anti-oxidant enzyme in MS. Neurons are thought to be not merely passive targets of microglia but rather control microglial activity through various signals including cytokines and chemokines. Soluble fractalkine (sFKN), which is secreted from damaged neurons by glutamate, promotes microglial phagocytosis of neuronal debris, and induces the antioxidant enzyme heme oxygenase-1 in microglia. IL-34 secreted from neurons also induces microglial neuroprotection. Astrocytes exert neuroprotective effect. However, toll-like receptor ligands induce neurotoxic molecules in astrocytes. IL-33 produced by astrocytes induces microglial activation. Thus, disruption of beneficial interaction between glia and neurons is crucial for the pathogenesis of MS.
Full Text of this Article in Japanese PDF (139K)
(臨床神経, 51：892−893, 2011)
key words：neuritic beading，ミクログリア，フラクタルカイン，IL-34
（受付日：2011年5月19日）
