Ahmed Sohel, Tsukahara Shinji, Yamamoto Shoji, Kunugita Naoki, Arashidani Keiichi, Fujimaki Hidekazu
Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Ibaraki, Japan.
J Neuroimmunol. 2007 May;186(1-2):104-11. doi: 10.1016/j.jneuroim.2007.03.010. Epub 2007 Apr 16.
We examined the effects of inhalative exposure to formaldehyde (FA, 400 ppb) on N-methyl-D-aspartate (NMDA) receptor subunits (NR2A and NR2B), dopamine receptor subtypes (D1 and D2), cyclic AMP responsive element-binding protein (CREB)-1, CREB-2, FosB/DeltaFosB, and transient receptor potential vanilloid receptor (TRPV1) in the hippocampus of ovalbumin-immunized mice using quantitative real-time PCR. Western blot analyses for pCREB were performed. The mRNA levels of NR2A, D1 and D2 receptors, and CREB-1 were significantly increased by FA, but NR2B, CREB-2, FosB/DeltaFosB, and TRPV1 mRNA levels remained unchanged. Treatment with MK-801 normalized the mRNA levels induced by FA. There was no significant effect of FA exposure and MK-801 treatment on the protein level of pCREB. These results indicate that FA exposure selectively up-regulates hippocampal gene expression in immunologically sensitized mice. The FA effects are presumably mediated by glutamatergic neurotransmission through NMDA receptors.
我们使用定量实时聚合酶链反应，研究了吸入甲醛（FA，400 ppb）对卵清蛋白免疫小鼠海马中N-甲基-D-天冬氨酸（NMDA）受体亚基（NR2A和NR2B）、多巴胺受体亚型（D1和D2）、环磷酸腺苷反应元件结合蛋白（CREB）-1、CREB-2、FosB/DeltaFosB以及瞬时受体电位香草酸受体（TRPV1）的影响。进行了磷酸化CREB的蛋白质印迹分析。FA使NR2A、D1和D2受体以及CREB-1的mRNA水平显著升高，但NR2B、CREB-2、FosB/DeltaFosB和TRPV1的mRNA水平保持不变。用MK-801处理可使FA诱导的mRNA水平恢复正常。FA暴露和MK-801处理对磷酸化CREB的蛋白质水平没有显著影响。这些结果表明，FA暴露在免疫致敏小鼠中选择性地上调海马基因表达。FA的作用可能是通过NMDA受体介导的谷氨酸能神经传递实现的。
