Abstract
Purpose1-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. MethodsFour groups of 12 male Wistar rats were exposed to 0, 400, 800, 1000ppm 1-BP, 8h/day for 7 days. Another four groups of six rats each were exposed to 0, 400, 800 and 1000ppm 1-BP for 2 weeks followed by 0, 200, 400 and 800ppm for another 2 weeks, respectively. Another four groups of six rats each were exposed to 0, 200, 400 and 800ppm 1-BP for 4 weeks. Rats were injected with 5-bromo-2′-deoxy-uridine (BrdU) after 4-week exposure at 1000/800ppm 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. ResultsBrdU-positive cells were significantly lower in the 800/1000ppm-4-week group than the control. 1-Week exposure to 1-BP at 800 and 1000ppm significantly reduced noradrenalin level in the striatum. Four-week exposure at 800ppm significantly decreased noradrenalin levels in the hippocampus, prefrontal cortex and striatum. 1-BP also reduced hippocampal BDNF and GR mRNA levels. ConclusionLong-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.
Published Version
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