Inhibition of MAPK/ERK signaling blocks hippocampal neurogenesis and impairs cognitive performance in prenatally infected neonatal rats
Inhibition of MAPK/ERK signaling blocks hippocampal neurogenesis and impairs cognitive performance in prenatally infected neonatal rats
复制标题
MAPK/ERK 信号传导的抑制会阻断海马神经发生并损害产前感染的新生大鼠的认知能力。
DOI：
10.1007/s00406-015-0588-y
复制
发表时间：
2015-09-01
影响因子：
4.7
通讯作者：
Yu, Huimin
中科院分区：
文献类型：
--
作者：
Jiang, Peifang;Zhu, Tao;Yu, Huimin
海马内源性神经发生被认为在脑损伤后的恢复中起着有利的作用。然而，其潜在的分子机制尚未得到充分的解释。在这里，我们调查了潜在的调节能力的MAPK/ERK信号对神经发生和相关的认知性能在产前感染的新生大鼠。从我们的数据来看，宫内感染可以诱导海马神经元凋亡，并通过唤起神经干细胞增殖和存活来促进内源性修复。我们还发现宫内感染可诱导p-ERK、p-CREB和BDNF水平升高，这可能与潜在的内源性拯救系统有关。抑制MAPK/ERK信号通路可加重海马神经元凋亡，减少神经发生，影响子代的认知能力，并下调p-ERK、p-CREB和BDNF的表达。我们的数据强烈表明，MAPK/ERK信号的激活可能通过抗凋亡机制在促进新生成的神经干细胞的存活中发挥重要作用，这可能在与产前感染大鼠的认知能力发展相关的内源性神经保护中特别重要。
Hippocampus endogenous neurogenesis has been postulated to play a favorable role in brain restoration after injury. However, the underlying molecular mechanisms have been insufficiently deciphered. Here we investigated the potential regulatory capacity of MAPK/ERK signaling on neurogenesis and the associated cognitive performance in prenatally infected neonatal rats. From our data, intrauterine infection could induce hippocampal neuronal apoptosis and promote endogenous repair by evoking neural stem cell proliferation and survival. We also found intrauterine infection could induce increased levels of p-ERK, p-CREB and BDNF, which might be responsible for the potential endogenous rescue system. Furthermore, inhibition of MAPK/ERK signaling could aggravate hippocampal neuronal apoptosis, decrease neurogenesis, and impair the offspring's cognitive performances and could also down-regulate the levels of p-ERK, p-CREB and BDNF. Our data strongly suggest that the activation of MAPK/ERK signaling may play a significant role in promoting survival of newly generated neural stem cells via an anti-apoptotic mechanism, which may be particularly important in endogenous neuroprotection associated with cognitive performance development in prenatally infected rats.