Toluene inhibits hippocampal neurogenesis in adult mice.
Toluene, a representative industrial solvent and abused inhalant, decreases neuronal activity in vitro and causes mental depression and cognitive impairment in humans. However, the effects of toluene on brain function and the sites of its action are poorly understood. This study investigated the temporal changes of neurogenesis in the hippocampus of adult C57BL/6 mice after acute administration of toluene using two immunohistochemical markers for neurogenesis, Ki-67 and doublecortin (DCX). In addition, after toluene treatment, depression-like behaviors and learning and memory tasks were examined to assess hippocampal neurogenesis-related behavioral dysfunction. The number of Ki-67- and DCX-positive cells in the dentate gyrus of adult hippocampi declined acutely between 0 h and 24 h after toluene treatment (500 mg/kg, i.p.) and increased gradually from 2 to 8 days post-administration. The level of Ki-67 and DCX immunoreactivity decreased in a dose-dependent manner within the range of toluene administered (0-1000 mg/kg). In tail suspension and forced-swim tests performed at 1 and 4 days after toluene treatment (500 mg/kg), mice showed significant depression-like behaviors compared to the vehicle-treated controls. In the contextual fear conditioning and object recognition memory test, the mice trained at 1 and 4 days after toluene treatment showed significant memory defects compared to the vehicle-treated controls. This study suggests that acute exposure to toluene reduces the rate of adult hippocampal neurogenesis and can cause hippocampal dysfunction such as depression and cognitive impairment.
Seo
Heung-Sik
HS
Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
Yang
Miyoung
M
Song
Myoung-Sub
MS
Kim
Joong-Sun
JS
Kim
Sung-Ho
SH
Kim
Jong-Choon
JC
Kim
Heechul
H
Shin
Taekyun
T
Wang
Hongbing
H
Moon
Changjong
C
D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D046353:Immobility Response, Tonic / Q000187:drug effects; D019394:Ki-67 Antigen / Q000378:metabolism; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D012997:Solvents / Q000633:toxicity*; D014050:Toluene / Q000633:toxicity*
C000714328:DCX protein, human; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D012997:Solvents; D014050:Toluene