title: Effects of sub-acute and sub-chronic inhalation of 1-bromopropane on neurogenesis in adult rats.
abstract: OBJECTIVE
  1-Bromopropane (1-BP) intoxication is associated with depression and cognitive and memory deficits. The present study tested the hypothesis that 1-BP suppresses neurogenesis in the dentate gyrus, which is involved in higher cerebral function, in adult rats.
  
  
  METHODS
  Four groups of 12 male Wistar rats were exposed to 0, 400, 800, 1000 ppm 1-BP, 8 h/day for 7 days. Another four groups of six rats each were exposed to 0, 400, 800 and 1000 ppm 1-BP for 2 weeks followed by 0, 200, 400 and 800 ppm for another 2 weeks, respectively. Another four groups of six rats each were exposed to 0, 200, 400 and 800 ppm 1-BP for 4 weeks. Rats were injected with 5-bromo-2'-deoxy-uridine (BrdU) after 4-week exposure at 1000/800 ppm to examine neurogenesis in the dentate gyrus by immunostaining. We measured factors known to affect neurogenesis, including monoamine levels, and mRNA expression levels of brain-derived neurotrophic factor (BDNF) and glucocorticoid receptor (GR), in different brain regions.
  
  
  RESULTS
  BrdU-positive cells were significantly lower in the 800/1000 ppm-4-week group than the control. 1-Week exposure to 1-BP at 800 and 1000 ppm significantly reduced noradrenalin level in the striatum. Four-week exposure at 800 ppm significantly decreased noradrenalin levels in the hippocampus, prefrontal cortex and striatum. 1-BP also reduced hippocampal BDNF and GR mRNA levels.
  
  
  CONCLUSIONS
  Long-term exposure to 1-BP decreased neurogenesis in the dentate gyrus. Downregulation of BDNF and GR mRNA expression and low hippocampal norepinephrine levels might contribute, at least in part, to the reduced neurogenesis.
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Lingyi
authors.initials: L
authors.lastname: Zhang
authors.forename: Taku
authors.initials: T
authors.lastname: Nagai
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ibi
authors.forename: Sahoko
authors.initials: S
authors.lastname: Ichihara
authors.forename: Kaviarasan
authors.initials: K
authors.lastname: Subramanian
authors.forename: Zhenlie
authors.initials: Z
authors.lastname: Huang
authors.forename: Sahabudeen Sheik
authors.initials: SS
authors.lastname: Mohideen
authors.forename: Hisao
authors.initials: H
authors.lastname: Naito
authors.forename: Gaku
authors.initials: G
authors.lastname: Ichihara
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006842:Hydrocarbons, Brominated / Q000008:administration & dosage / Q000633:toxicity; D019570:Inhalation Exposure; D008297:Male; D055495:Neurogenesis / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000235:genetics; D012997:Solvents / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D006842:Hydrocarbons, Brominated; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D012997:Solvents; D009638:Norepinephrine; C118559:1-bromopropane