Effects of sub-acute and sub-chronic inhalation of 1-bromopropane on neurogenesis in adult rats

Lingyi Zhang, Taku Nagai, Kiyofumi Yamada, Daisuke Ibi, Sahoko Ichihara, Kaviarasan Subramanian, Zhenlie Huang, Sahabudeen Sheik Mohideen, Hisao Naito, Gaku Ichihara

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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.

Original languageEnglish
Pages (from-to)76-82
Number of pages7
JournalToxicology
Volume304
DOIs
Publication statusPublished - 08-02-2013

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All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Zhang, L., Nagai, T., Yamada, K., Ibi, D., Ichihara, S., Subramanian, K., Huang, Z., Mohideen, S. S., Naito, H., & Ichihara, G. (2013). Effects of sub-acute and sub-chronic inhalation of 1-bromopropane on neurogenesis in adult rats. Toxicology, 304, 76-82. https://doi.org/10.1016/j.tox.2012.12.009