Nitta Atsumi, Zheng Wen-Hua, Quirion Rémi
Department of Psychiatry, McGill University, Verdun-Montreal, PQ, Canada.
J Neurosci Res. 2004 Apr 1;76(1):98-103. doi: 10.1002/jnr.20057.
Corticosterone (CORT) is well known to induce neuronal damage in various brain regions including the hippocampus, but the precise mechanism(s) of action underlying these effects has yet to be fully established. Insulin-like growth factor-1 (IGF-1) is a trophic factor promoting cell survival by the activation of the phosphatidylinositide 3-kinase (PI3K)/Akt kinase pathway. We report that IGF-1 prevents neuronal cell death induced by CORT, likely via the stimulation of the PI3K/Akt pathway in primary hippocampal cultured neurons. CORT induced neuronal cell death at a minimal concentration of 50 nM. IGF-1 (10 nM) prevented cell death induced by CORT under serum-free conditions. The neuroprotective effect of IGF-1 was accompanied by reversal of the Akt pathway inhibition induced by CORT. The PI3 kinase inhibitor, LY29004, inhibited the neuroprotective effect of IGF-1 whereas the MEK (MAPK kinase) inhibitor PD98059, an upstream blocker of mitogen-activated protein (MAP) kinase, had no effect. These results suggest that IGF-1 can prevent neuronal cell death induced by CORT in hippocampal neurons by modulating the activity of the PI3K/Akt pathway.
众所周知，皮质酮（CORT）可在包括海马体在内的各个脑区诱导神经元损伤，但其产生这些作用的确切作用机制尚未完全明确。胰岛素样生长因子-1（IGF-1）是一种营养因子，通过激活磷脂酰肌醇3激酶（PI3K）/Akt激酶途径促进细胞存活。我们报告称，IGF-1可能通过刺激原代海马体培养神经元中的PI3K/Akt途径，防止CORT诱导的神经元细胞死亡。CORT在最低浓度为50 nM时诱导神经元细胞死亡。IGF-1（10 nM）在无血清条件下可防止CORT诱导的细胞死亡。IGF-1的神经保护作用伴随着CORT诱导的Akt途径抑制的逆转。PI3激酶抑制剂LY29004抑制了IGF-1的神经保护作用，而促分裂原活化蛋白（MAP）激酶的上游阻滞剂MEK（MAPK激酶）抑制剂PD98059则没有作用。这些结果表明，IGF-1可通过调节PI3K/Akt途径的活性，防止海马体神经元中CORT诱导的神经元细胞死亡。
