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NEUROPHARMACOLOGY

Arundic Acid Ameliorates Cerebral Amyloidosis and Gliosis in Alzheimer Transgenic Mice

Institute of Medical Science, Saitama Medical School, Kawagoe, Saitama, Japan (T.M., T.T., J.T., T.A.); Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut (T.T.); Neuroimmunology Laboratory, Silver Child Development Center, Department of Psychiatry and Behavioral Medicine, University of South Florida College of Medicine, Tampa, Florida (J.T.); Immuno-Biological Laboratories Co., Ltd., Fujioka, Gunma, Japan (Y.H.); and Minase Research Institute, Ono Pharmaceutical Co., Ltd., Mishima, Osaka, Japan (N.Y., J.Y., T.S., Y.K., N.T.)

Like microglia, reactive astrocytes produce a myriad of neurotoxic substances in various brain pathologies, such as Alzheimer's disease (AD), trauma, and cerebral ischemia. Among the numerous products of reactive astrocytes, attention has recently been directed toward the possible detrimental role of S100B, because the protein has been shown to be highly expressed along with the progression of brain damage and to exert neurotoxic effects at high concentrations. The present study aimed to examine the possible role of astrocyte-derived S100B in the progression of cerebral amyloidosis and gliosis in transgenic mice overproducing mutant amyloid precursor protein (Tg APP_sw mice, line 2576). For this purpose, arundic acid (Ono Pharmaceutical Co., Ltd., Mishima, Osaka, Japan), which is known to negatively regulate astrocyte synthesis of S100B, was orally administered to Tg APP_sw mice for 6 months from 12 months of age, and the effects of the agent on the above parameters were examined. Here, we report that -amyloid deposits along with amyloid- peptide/S100B levels, as well as -amyloid plaque-associated reactive gliosis (astrocytosis and microgliosis), were significantly ameliorated in arundic acid-treated Tg APP_sw mice relative to vehicle-treated Tg APP_sw mice at 19 months of age. Based on the above results, arundic acid is considered to deserve further exploration as a promising therapeutic agent for AD.

Address correspondence to: Dr. Takao Asano or Dr. Takashi Mori, Institute of Medical Science, Saitama Medical School, 1981 Kamoda, Kawagoe, Saitama 350-8550, Japan. E-mails: asano{at}saitama-med.ac.jp or t_mori{at}saitamamed.ac.jp

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