Astrocyte-conditioned medium protecting hippocampal neurons in primary cultures against corticosterone-induced damages via PI3-K/Akt signal pathway.
Prolonged or excessive exposure to corticosterone leads to neuronal damages in the brain regions, including hippocampus. We reported that astrocyte-conditioned medium (ACM) protected the neurons of the primary hippocampal cultures against the corticosterone-induced damages. Corticosterone added to the cultures resulted in a significant number of TUNEL-positive cells. However, corticosterone-induced TUNEL labeling was suppressed as for ACM-cultured neurons. To delineate the molecular basis underlying the neuroprotection of ACM, we assessed the activation of ERK1/2 and (PI3-K)/Akt signal pathways in response to corticosterone-induced neuronal damages. Western blot test revealed that corticosterone increased the phosphorylation of ERK1/2 and PI3-K/Akt in hippocampal neurons grown in Neurobasal medium supplemented with B27 and 500 microm L-glutamine (NBM+). Interestingly, the increase of phospho-ERK1/2 and Akt levels was much pronounced and the time course of phosphorylation was altered in ACM, suggesting that both signaling pathways might participate in ACM protection. Furthermore, the selective inhibitor of Akt, rather than ERK1/2, blocked the neuroprotective activity against corticosterone in ACM-cultured neurons. In summary, our data showed that ACM had a potent neuroprotective effect in cultured neurons. PI3-K/Akt signal pathway, but not ERK1/2, was involved in the protective activity against the corticosterone-induced damages.
Zhu
Ze-Hua
ZH
Department of Integrative Medicine and Neurobiology, Institute of Acupuncture Research, Shanghai Medical College, Fudan University, P.O. Box 291 138, Yi Xue Yuan Road, Shanghai 200032, PR China.
Yang
Ru
R
Fu
Xin
X
Wang
Yan-Qing
YQ
Wu
Gen-Cheng
GC
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000737:chemistry*; D002478:Cells, Cultured; D003345:Corticosterone / Q000009:adverse effects*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000166:cytology*; D020287:In Situ Nick-End Labeling / Q000379:methods; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D048052:Mitogen-Activated Protein Kinase 3; D003345:Corticosterone