title: Glial activation with concurrent up-regulation of inflammatory mediators in trimethyltin-induced neurotoxicity in mice.
abstract: Trimethyltin (TMT), a potent neurotoxic chemical, causes dysfunction and neuroinflammation in the brain, particularly in the hippocampus. The present study assessed TMT-induced glial cell activation and inflammatory cytokine alterations in the mouse hippocampus, BV-2 microglia, and primary cultured astrocytes. In the mouse hippocampus, TMT treatment significantly increased the expression of glial cell markers, including the microglial marker ionized calcium-binding adapter molecule 1 and the astroglial marker glial fibrillary acidic protein. The expression of M1 and M2 microglial markers (inducible nitric oxide synthase [iNOS] and CD206, respectively) and pro-inflammatory cytokines (interleukin [IL]-1β, IL-6 and tumor necrosis factor [TNF]-α) were significantly increased in the mouse hippocampus following TMT treatment. In BV-2 microglia, iNOS, IL-1β, TNF-α, and IL-6 expression increased significantly, whereas arginase-1 and CD206 expression decreased significantly after TMT treatment in a time- and concentration-dependent manner. In primary cultured astrocytes, iNOS, arginase-1, IL-1β, TNF-α, and IL-6 expression increased significantly, whereas IL-10 expression decreased significantly after TMT treatment in a time- and concentration-dependent manner. These results indicate that significant up-regulation of pro-inflammatory signals in TMT-induced neurotoxicity may be associated with pathological processing of TMT-induced neurodegeneration.
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea; Center for Neuroscience, Korea Institute of Science and Technology (KIST), Seoul 136-791, South Korea.
authors.forename: Juhwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Miyoung
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Yeonghoon
authors.initials: Y
authors.lastname: Son
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Hyosun
authors.initials: H
authors.lastname: Jang
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Dongwoo
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Jong-Choon
authors.initials: JC
authors.lastname: Kim
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Animal Science, College of Agriculture and Life Science, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Man-Jong
authors.initials: MJ
authors.lastname: Kang
authors.affiliation: Center for Neuroscience, Korea Institute of Science and Technology (KIST), Seoul 136-791, South Korea.
authors.forename: Heh-In
authors.initials: HI
authors.lastname: Im
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University, Jeju 690-756, South Korea. Electronic address: shint@jejunu.ac.kr.
authors.forename: Taekyun
authors.initials: T
authors.lastname: Shin
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea. Electronic address: moonc@chonnam.ac.kr.
authors.forename: Changjong
authors.initials: C
authors.lastname: Moon
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014298:Trimethyltin Compounds / Q000494:pharmacology*
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D014298:Trimethyltin Compounds; C046488:trimethyltin
keywords: Cytokine; Glial activation; Hippocampus; Neuroinflammation; Trimethyltin