Sakai N, Yamada M, Numakawa T, Ogura A, Hatanaka H
Institute for Protein Research, Osaka University, Suita, Japan.
Brain Res. 1997 Dec 19;778(2):318-28. doi: 10.1016/s0006-8993(97)01052-4.
Brain-derived neurotrophic factor (BDNF) is thought to regulate neuronal plasticity in developing and matured neurons, although the molecular mechanisms are less well characterized. We monitored changes in the intracellular calcium (Ca2+) levels induced by BDNF using a fluorescence Ca2+ indicator (Fluo-3) by means of confocal laser microscopy in rat cultured hippocampal neurons. BDNF acutely potentiated spontaneous Ca2+ oscillations in dendrites and also in the soma of several neurons, although it increased intracellular Ca2+ in only selective proportion of resting neurons without Ca2+ oscillations. The potentiation was observed both in the frequency and the amplitude of Ca2+ oscillations, completely blocked by K-252a, and significantly reduced by 2-aminophosphonovaleric acid. These findings suggest that BDNF increases glutamate release and N-methyl-D-aspartate (NMDA) channel-gated Ca2+ influx via TrkB and regulates the frequency and the amplitude of Ca2+ oscillations. BDNF may have the potential to modulate spontaneous Ca2+ oscillations to regulate neuronal plasticity in developing hippocampal neurons.
脑源性神经营养因子(BDNF)被认为可调节发育中和成熟神经元的神经可塑性,尽管其分子机制尚不完全清楚。我们通过共聚焦激光显微镜,使用荧光钙指示剂(Fluo-3)监测了BDNF在大鼠培养海马神经元中诱导的细胞内钙(Ca2+)水平变化。BDNF可急性增强多个神经元树突及胞体中的自发性Ca2+振荡,尽管它仅在无Ca2+振荡的静息神经元的选择性比例中增加细胞内Ca2+。在Ca2+振荡的频率和幅度上均观察到了增强作用,K-252a可完全阻断该作用,而2-氨基膦酰戊酸可显著降低该作用。这些发现表明,BDNF通过TrkB增加谷氨酸释放和N-甲基-D-天冬氨酸(NMDA)通道门控的Ca2+内流,并调节Ca2+振荡的频率和幅度。BDNF可能具有调节自发性Ca2+振荡以调控发育中海马神经元神经可塑性的潜力。