title: Amphotericin B induces glial cell line-derived neurotrophic factor in the rat brain.
abstract: Amphotericin B (AmB) is a polyene antifungal drug and is reported to be one of a few reagents having therapeutic effects on prion diseases, that is, a delay in the appearance of clinical signs and prolongation of the survival time in an animal model. In prion diseases, glial cells have been suggested to play important roles; however, the therapeutic mechanism of AmB on prion diseases remains elusive. We have previously reported that AmB changed the expression of neurotrophic factors in microglia and astrocytes (Motoyoshi et al., 2008, Neurochem. Int. 52, 1290-1296; Motoyoshi-Yamashiro et al., 2013, ibid. 63, 93-100). These results suggested that neurotrophic factors derived from glial cells might be involved in the therapeutic mechanism of AmB. In the present study, we examined immunohistochemically the effects of AmB on the expression of neurotrophic factors in the rat brain. We found that direct injection of AmB into the striatum significantly enhanced the expression of glial cell line-derived neurotrophic factor protein. Amphotericin B also increased the expressions of CD11b and glial fibrillary acidic protein, markers of microglia and astrocytes, respectively. Moreover, expressions of the two neurotrophic factors by AmB were co-localized with the expression of CD11b or glial fibrillary acidic protein. These results suggest that AmB in vivo might also activate glial cells and induce the production of neurotrophic factors protecting neurons in prion diseases.
authors.affiliation: Laboratory of Integrative Physiology in Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka 598-8531, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Motoyoshi-Yamashiro
authors.forename: Katsura
authors.initials: K
authors.lastname: Takano
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawabe
authors.forename: Takeshi
authors.initials: T
authors.lastname: Izawa
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Nakajima
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Moriyama
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000935:Antifungal Agents; D015415:Biomarkers; D039481:CD11b Antigen; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D000666:Amphotericin B