TY - JOUR
T1 - Effects of global ischemia and estradiol pretreatment on phosphorylation of Akt, CREB and STAT3 in hippocampal CA1 of young and middle-aged female rats
AU - De Butte-Smith, M.
AU - Zukin, R. S.
AU - Etgen, A. M.
N1 - Funding Information:
The authors gratefully acknowledge support by DHHS Grant R01 AG027702 to A.M.E., D.P. Purpura Department of Neuroscience, Albert Einstein College of Medicine and the F.M. Kirby Program in Neural Repair and Protection. The authors would also like to thank Mr. Fabrizio Pontarelli and Ms. Adrianna Latuszek for their technical assistance.
PY - 2012/8/30
Y1 - 2012/8/30
N2 - Transient global ischemia induces selective, delayed neuronal death of pyramidal neurons in the hippocampal CA1. Whereas long term treatment of middle-aged female rats with estradiol at physiological doses ameliorates neuronal death, the signaling pathways that mediate the neuroprotection are, as yet, unknown. Protein kinase B (Akt) and downstream transcription factors, the cAMP response element binding protein (CREB) and signal transducer and activator of transcription (STAT3) are critical players in cellular survival following injury. The present study was undertaken to determine whether long term estradiol alters the phosphorylation status and activity of Akt, STAT3 and CREB in ovariohysterectomized, middle-aged and young female rats subjected to global ischemia. Irrespective of either hormone or ischemic condition, middle-aged females exhibited lower levels of p-CREB and higher levels of Akt and STAT3 in CA1 than young females, as assessed by Western blot. In middle-aged animals, ischemia increased the phosphorylation status/activity of Akt and STAT3, and decreased the phosphorylation status/activity of CREB in the hippocampal CA1. Whereas estradiol did not detectably alter the phosphorylation status/activity of Akt or STAT3, it prevented the ischemia-induced decrease in nuclear p-CREB. Similar results were observed for the young females. Collectively, these data demonstrate that CREB, STAT3, and Akt are involved in the molecular response to global ischemia and that age influences the status of CREB, STAT3 and Akt activity in CA1 under physiological as well as pathological conditions, further emphasizing the importance of including older rodents in neuroprotection studies.
AB - Transient global ischemia induces selective, delayed neuronal death of pyramidal neurons in the hippocampal CA1. Whereas long term treatment of middle-aged female rats with estradiol at physiological doses ameliorates neuronal death, the signaling pathways that mediate the neuroprotection are, as yet, unknown. Protein kinase B (Akt) and downstream transcription factors, the cAMP response element binding protein (CREB) and signal transducer and activator of transcription (STAT3) are critical players in cellular survival following injury. The present study was undertaken to determine whether long term estradiol alters the phosphorylation status and activity of Akt, STAT3 and CREB in ovariohysterectomized, middle-aged and young female rats subjected to global ischemia. Irrespective of either hormone or ischemic condition, middle-aged females exhibited lower levels of p-CREB and higher levels of Akt and STAT3 in CA1 than young females, as assessed by Western blot. In middle-aged animals, ischemia increased the phosphorylation status/activity of Akt and STAT3, and decreased the phosphorylation status/activity of CREB in the hippocampal CA1. Whereas estradiol did not detectably alter the phosphorylation status/activity of Akt or STAT3, it prevented the ischemia-induced decrease in nuclear p-CREB. Similar results were observed for the young females. Collectively, these data demonstrate that CREB, STAT3, and Akt are involved in the molecular response to global ischemia and that age influences the status of CREB, STAT3 and Akt activity in CA1 under physiological as well as pathological conditions, further emphasizing the importance of including older rodents in neuroprotection studies.
KW - Akt
KW - Estradiol
KW - Global ischemia
KW - Hippocampus
KW - Neuroprotection
KW - Ovariectomy
KW - Signal transducer and activator of transcription-3
KW - cAMP response element binding protein
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U2 - 10.1016/j.brainres.2012.06.036
DO - 10.1016/j.brainres.2012.06.036
M3 - Article
C2 - 22771860
AN - SCOPUS:84864652658
SN - 0006-8993
VL - 1471
SP - 118
EP - 128
JO - Brain research
JF - Brain research
ER -