Abstract

Alzheimer's disease (AD), the most relevant cause of dementia in elderly, is characterized by amyloid beta (A beta) containing plaques and neurofibrillatory tangles, synaptic and neuronal loss, along with progressive cognitive impairment in short-term memory. However, mechanistic links between protein kinase A (PKA), oxidative stress and memory loss in response to A beta remain elusive. In the present study, we examined the effects of post-training bilateral intra-hippocampal infusions of the specific protein kinase All inhibitor, H-89, on memory deficits induced by A beta (1-42) in A beta-pretreated rats. H-89 and A beta were administered immediately after completion of training. All animals were trained for 4 consecutive days and tested 9 and 19 days after the infusions. Significant differences were observed in the time and distance of finding the hidden platform in A beta treated animals after 19 days. Interestingly, intra-hippocampal infusion of H-89 (5 mu M/side) significantly prevented the A beta-induced memory impairment. Furthermore, evaluation of NF kappa B (nuclear factor-kappa B), and antioxidant enzymes, such as gamma-GCS (glutamylcysteine synthetase), HO-1 (hemeoxygenase-1), GSH (glutathione), and SOD (superoxide dismutase) confirmed the protective effect of H-89. Given the possible neuroprotective effects of H-89 on A beta-induced memory impairment, our results may open a new avenue for the prevention of AD by PKAII signaling pathway inhibitor. (C) 2011 Elsevier B.V. All rights reserved.