Involvement of P38MAPK activation by NMDA receptors and non-NMDA receptors in amyloid-β peptide-induced neuronal loss in rat hippocampal CA1 and CA3 subfields

Oligomeric amyloid-beta peptide (A beta) has been found to be associated with the pathogenesis of Alzheimer's disease (AD). Numerous studies have reported A beta neurotoxicity, but the underlying molecular mechanisms remain to be fully illuminated. In the present study, we investigated the A beta-induced activation and regulation of P38MAPKs in rat hippocampus in vivo. The results showed that intracerebroventricular injection of oligomeric A beta 25-35 increased the activation (phosphorylation) of P38MAPKs, and the level of cleaved caspase-3, but decreased the number of neurons in rat hippocampal CA1 and CA3 subfields. Downregulation of P38MAPK activity by SB239063 protected against the A beta neurotoxicity. Pretreatment with NMDA and non-NMDA receptor antagonists respectively suppressed P38MAPK activation induced by A beta 25-35 oligomers and presented neuroprotective effect. Taken together, these data suggest that P38MAPK activation via NMDA and non-NMDA receptors is a key signal cascade in A beta-induced neuronal death. Inhibition of P38MAPK cascades may be a promising treatment in AD. (C) 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.