Insulin-like growth factor 1 prevents neuronal cell death induced by corticosterone through activation of the PI3k/Akt pathway.
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.
Nitta
Atsumi
A
Department of Psychiatry, McGill University, Verdun-Montreal, PQ, Canada.
Zheng
Wen-Hua
WH
Quirion
Rémi
R
D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003345:Corticosterone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D015682:Retroviridae Proteins, Oncogenic / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*
D003345:Corticosterone; D004791:Enzyme Inhibitors; D007334:Insulin-Like Growth Factor I; D020928:Mitogen-Activated Protein Kinases; D018696:Neuroprotective Agents; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015682:Retroviridae Proteins, Oncogenic