Sakaue Motoharu, Mori Naoko, Makita Misato, Fujishima Kana, Hara Shuntaro, Arishima Kazuyoshi, Yamamoto Masako
Department of Anatomy II, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara 229-8501, Japan.
Brain Res. 2009 Jun 1;1273:155-62. doi: 10.1016/j.brainres.2009.03.035. Epub 2009 Mar 28.
Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor (NGF) family and has been shown to promote neuronal survival and contribute to neural development. Although methylmercury, a neurotoxin, induces the cell death of neurons in vitro, there is little information regarding the effects of neurotrophins on the methylmercury-induced cell death of neurons. In the present study, we investigated the effect of BDNF on methylmercury-induced cell death in a primary culture of rat cerebellar granular cells. BDNF increased the viability of the cultured cells when treated alone, but unexpectedly accelerated the cell death induced by administration of methylmercury. Among other growth factors tested, only neurotrophin-4 (NT-4) demonstrated a similar acceleration of methylmercury-induced cell death. The cell death-accelerating effect of BDNF was inhibited by a BDNF-neutralizing antibody or a MAPK inhibitor. To determine whether the effect of BDNF occurs via TrkB, a receptor of BDNF and NT-4, we investigated the effects of BDNF and methylmercury in a TrkB transformant of rat neuroblastoma B35 cells. The methylmercury-induced cell death of the TrkB transformant was accelerated by BDNF, while that of the mock transformant was not. These results indicate that BDNF accelerates methylmercury-induced cell death via TrkB, at least in vitro, and suggest that BDNF and TrkB may also contribute to the sensitivity of neurons to methylmercury toxicity.
脑源性神经营养因子（BDNF）是神经生长因子（NGF）家族的成员之一，已被证明可促进神经元存活并有助于神经发育。虽然神经毒素甲基汞在体外可诱导神经元细胞死亡，但关于神经营养因子对甲基汞诱导的神经元细胞死亡的影响却知之甚少。在本研究中，我们调查了BDNF对大鼠小脑颗粒细胞原代培养物中甲基汞诱导的细胞死亡的影响。单独处理时，BDNF可提高培养细胞的活力，但出乎意料的是，它会加速甲基汞给药诱导的细胞死亡。在测试的其他生长因子中，只有神经营养因子4（NT-4）表现出类似的加速甲基汞诱导的细胞死亡的作用。BDNF的细胞死亡加速作用被BDNF中和抗体或丝裂原活化蛋白激酶（MAPK）抑制剂所抑制。为了确定BDNF的作用是否通过其受体TrkB发生，TrkB是BDNF和NT-4的受体，我们研究了BDNF和甲基汞在大鼠神经母细胞瘤B35细胞的TrkB转化体中的作用。BDNF加速了TrkB转化体中甲基汞诱导的细胞死亡，而mock转化体则没有。这些结果表明，至少在体外，BDNF通过TrkB加速甲基汞诱导的细胞死亡，并提示BDNF和TrkB可能也会影响神经元对甲基汞毒性的敏感性。
