title: Involvement of BDNF/ERK signaling in spontaneous recovery from trimethyltin-induced hippocampal neurotoxicity in mice.
abstract: Trimethyltin (TMT) toxicity causes histopathological damage in the hippocampus and induces seizure behaviors in mice. The lesions and symptoms recover spontaneously over time; however, little is known about the precise mechanisms underlying this recovery from TMT toxicity. We investigated changes in the brain-derived neurotrophic factor/extracellular signal-regulated kinases (BDNF/ERK) signaling pathways in the mouse hippocampus following TMT toxicity. Mice (7 weeks old, C57BL/6) administered TMT (2.6 mg/kg intraperitoneally) showed acute and severe neurodegeneration with increased TUNEL-positive cells in the dentate gyrus (DG) of the hippocampus. The mRNA and protein levels of BDNF in the hippocampus were elevated by TMT treatment. Immunohistochemical analysis showed that TMT treatment markedly increased phosphorylated ERK1/2 expression in the mouse hippocampus 1-4 days after TMT treatment, although the intensity of ERK immunoreactivity in mossy fiber decreased at 1-8 days post-treatment. In addition, ERK-immunopositive cells were localized predominantly in doublecortin-positive immature progenitor neurons in the DG. In primary cultured immature hippocampal neurons (4 days in vitro), BDNF treatment alleviated TMT-induced neurotoxicity, via activation of the ERK signaling pathway. Thus, we suggest that BDNF/ERK signaling pathways may be associated with cell differentiation and survival of immature progenitor neurons, and will eventually lead to spontaneous recovery in TMT-induced hippocampal neurodegeneration.
authors.affiliation: College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Sueun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-740, South Korea.|Department of Physiology and Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Miyoung
authors.initials: M
authors.lastname: Yang
authors.affiliation: College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Juhwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Yeonghoon
authors.initials: Y
authors.lastname: Son
authors.affiliation: College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Jinwook
authors.initials: J
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Sohi
authors.initials: S
authors.lastname: Kang
authors.affiliation: College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Wooseok
authors.initials: W
authors.lastname: Ahn
authors.affiliation: College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Jong-Choon
authors.initials: JC
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Jeju National University, Jeju 690-756, South Korea.
authors.forename: Taekyun
authors.initials: T
authors.lastname: Shin
authors.affiliation: Department of Physiology and Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Changjong
authors.initials: C
authors.lastname: Moon
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006836:Hydro-Lyases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000150:complications / Q000209:etiology / Q000473:pathology*; D009570:Nitriles / Q000494:pharmacology; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D012640:Seizures / Q000209:etiology; D013997:Time Factors; D014298:Trimethyltin Compounds / Q000633:toxicity
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002070:Butadienes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009419:Nerve Tissue Proteins; D009570:Nitriles; D014298:Trimethyltin Compounds; C113580:U 0126; C046488:trimethyltin; D006836:Hydro-Lyases; C045581:lactate dehydratase; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: BDNF; ERK; Hippocampus; Spontaneous recovery; Trimethyltin