Inhibition of PKA attenuates memory deficits induced by β-amyloid (1-42), and decreases oxidative stress and NF-κB transcription factors

Alzheimer’s disease (AD), the most relevant cause of dementia in elderly, is characterized by amyloidβ (Aβ) containing plaques and neurofibrillatory tangles, synaptic and neurona  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 Aβ remain elusive. In the present study, is examined the effects of post-training bilateral intra-hippocampal infusions of the specific protein kinase AII inhibitor, H-89, on memory deficits induced by Aβ (1–42) in Aβ-pretreated rats. H-89 and Aβ 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 Aβ treated animals after 19 days. Interestingly, intra-hippocampal infusion of H-89 (5 M/side) significantly prevented the Aβ-induced memory impairment. Furthermore, evaluation of NFB (nuclear factor-B), and antioxidant enzymes, such as γ-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-induced memory impairment, our results may open a new avenue for the prevention of AD by PKAII signaling pathway inhibitor.