Abstract：
PURPOSE: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. CONCLUSION: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.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Zhang L,Nagai T,Yamada K,Ibi D,Ichihara S,Subramanian K,Huang Z,Mohideen SS,Naito H,Ichihara Gdoi
10.1016/j.tox.2012.12.009subject
Has Abstractpub_date
2013-02-08 00:00:00pages
76-82eissn
0300-483Xissn
1879-3185pii
S0300-483X(12)00428-3journal_volume
304pub_type
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