Delayed ischemic postconditioning protects hippocampal CA1 neurons by preserving mitochondrial integrity via Akt/GSK3β signaling

Caifeng Zhou, Jingyi Tu, Quanguang Zhang, Dongshuang Lu, Ying Zhu, Wenli Zhang, Fang Yang, Darrell W Brann, Ruimin Wang

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Abstract

Delayed ischemic postconditioning (Post C), which involves a brief ischemia followed by reperfusion 2 days after 8-10 min global cerebral ischemia (GCI), has been shown to exert a remarkable protection of the vulnerable hippocampal CA1 region of the brain and attenuation of behavioral deficits, although the mechanisms remain poorly understood. The purpose of the current study was to explore the effect of Post C upon mitochondrial integrity, cytochrome c release and Bax translocation as a potential key mechanism for Post C protection of the critical hippocampal CA1 region neurons. The results of the study revealed that ischemic Post C (3 min) administered 2 days after 8-min GCI exerted a robust preservation from GCI injury, as evidenced by the increase of NeuN-positive and the decrease of TUNEL-positive cells, as well as morphological features of mitochondrial integrity in the hippocampal CA1 region. We also found that Post C significantly blocked inner mitochondrial membrane potential depolarization, as shown by JC-1 staining, and attenuates cytochrome c release and Bax translocation induced by GCI. Pre-treatment of the PI3K inhibitor LY294002, 20 min prior to Post C, significantly attenuated Post C-induced elevation of p-Akt and p-GSK3β, as well as prevented Post C enhancement of mitochondrial integrity and Post C neuroprotection. The results suggest that phosphorylation of Akt and subsequent inactivation of GSK3β signaling is critical in mediating Post C beneficial effects upon mitochondrial integrity, function and neuroprotection following GCI injury.

Original languageEnglish (US)
Pages (from-to)749-758
Number of pages10
JournalNeurochemistry International
Volume59
Issue number6
DOIs
StatePublished - Nov 1 2011

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Keywords

  • Akt
  • GSK3β
  • Ischemic postconditioning
  • Mitochondrial integrity
  • Neuroprotection

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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