The ameliorating effect of exercise on long-term memory impairment and dendritic retraction via the mild activation of AMP-activated protein kinase in chronically stressed hippocampal CA1 neurons

[PURPOSE]: Chronic stress affects the neuronal architecture of hippocampal subfields including the Cornu Ammonis 1 (CA1) region, which governs long-term memory. Exercise exerts a beneficial effect on memory improvement via hippocampal AMP-activated protein kinase (AMPK) activation. However, the relationship between the two phenomena is poorly understood. This study used animal and cell culture experimental systems to investigate whether chronic stress-induced impairment of memory consolidation and maladaptation of the neuronal architecture in the hippocampal CA1 area is prevented by regular exercise through AMPK activation. [METHODS]: Mice underwent four weeks of treadmill running with or without a 6h/21d-restraint stress regimen, along with treatment with Compound C. Memory consolidation was assessed using the Morris Water Maze (MWM). Dendritic rearrangement of hippocampal CA1 neurons was evaluated using the Golgi-Cox stain and Sholl analysis. Additionally, the primary hippocampal culture system was adopted for in vitro experiments. [RESULTS]: Chronic stress-induced failure of memory retention and reduction in AMPK activation were ameliorated by the exercise regimen. Chronic stress-or repeated corticosterone (CORT)-provoked malformation of the neuronal architecture was also suppressed by both exercise and treatment with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). [CONCLUSION]: Chronic stress causes dendritic retraction among dorsal hippocampal CA1 neurons via the downregulation of AMPK activation, thereby leading to failure of memory retention. In contrast, regular exercise protects against chronic stress-evoked defects in memory consolidation and changes in neuronal morphology in the dorsal hippocampal CA1 area via mild activation of AMPK.