Down-regulation of Ras / Akt Signaling and Hippocampal Neuronal Death following Transient Global Ischemia-Reperfusion in Rat brain

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Apotosis is one of the components of delayed neuronal death in the hippocampal CA1 following transient cerebral ischemia. However, the precise signal transduction for inducing this type of death is not fully determined. Recent research has shown that oncogenis Ras protein plays a role in regulation of cell survival and death. We hypothesized that apoptosis in delayed neuronal death is regulated with Ras and its signaling cascades. We examined the temporal profile of Ras and its downstream cascade following transient forebrain ischemia (15 min) in rat brain. Neuronal death was inconsistetly observed in the CA1 of the hippocampus (HE staining) 2 days after ischemia, whereas most neurons in the CA1 showed marked damage 3 days ofter ischemia. These damaged neurons exhibited positive TdT dUTP nick end labeling staining. α-Fodrin breakdown product in the hippocampus increased time dependently, 2 days and 3 days after reperfusion (by 14 and 25 times for 145-, 150-kDa, and by 30-40% for 120-kDa, respectively). The amounts of Ras and phospho-Akt were significantly decreased by approximately 30-50%. The results suggest that delayed neuranal death in the hippocampal CA1 following transient forebrain ischemia is characterized by an apoptotic nature and associated with and inhibition of the Ras-Akt cascade.
Yamaguchi University School of Medicineの論文