The role of microglia on the development of neurological disorders

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In this study we focused to investigation of regulatory mechanisms of microglial functions to clarify the pathophysiology of inflammatory neurological disorders and to search new therapeutic strategies. In the central nervous system, microglia function as antigen presenting cells, and inflammatory cells to induce autoimmune diseases such as multiple sclerosis. We have found the microglia produce IL-12 family cytokines which regulate differentiation of T helper cells (Suzumura et al., 2003,Sonobe et al., 2005). One subpopulation of microglia, designated as type 2 microglia do not prouduce IL-12 family cytokines. For the treatment of MS, only interferon-β is available in JAPAN. We have shown that interferon-β enhances inflammatory functions of microglia which may related to the development of adverse effects including malaise, fever etc. Phosphodiesterase inhibitors, such as ibudilast, effectively inhibit pro-inflammatory effects of interferon-b, suggesting possible effects of combination therapy of interferon and phosphodiesterase inhibitors, for the treatment of MS (Kawanokuchi et al., 2004,Feng et al., 2004). Pituitary adenylate cyclase activating polypeptide(PACAP) and radical scavenger, edalabone also suppressed the pro-inflammatory functions of microgiia and ameliorate clinical scores of experimental autoimmune encephalomyelitis (Kato et al., 2004,Banno et al., 2005).Microglia are considered to play a critical role in induction of axonal damage. We have found that microglia disturbed energy production in neurons via secreting glutamate. Thus, suppression of glutamate production by activated microglia may be of use for the future strategy to treat MS patients.