Involuntary, Forced or Voluntary Exercise Can Ameliorate the Cognitive Deficits by Enhancing Levels of Hippocampal NMDAR1, Pampar1 and Pcamkii in a Model of Vascular Dementia

Objectives: To investigate the effect on vascular dementia of involuntary exercise induced by functional electrical stimulation and of forced and voluntary exercise, focusing on the recovery of cognitive function and using a rat model of dementia.Methods: A demential model was created in Wistar rats who were then given forced exercise, allowed voluntary exercise (wheel running) or had exercise induced through functional electrical stimulation. Their responses were quantified using a Morris water maze and by measuring long-term potentiation in the hippocampus. Immunohistochemical staining was used to evaluate neurogenesis in the hippocampus and Nissl staining was applied to visualize viable neuron loss in the DG sector. In addition, the levels of NMDAR1, AMPAR1, pAMPAR1, pCaMKII, CaMKII, Bcl-2 and Bax in the hippocampus were assessed by western blotting.Results: All of the exercise groups showed a recovery of cognitive performance and improved long-term potentiation. The three modes of exercise all increased the number of DCX immunopositive cells and reduced losses of intact-appearing neurons in the hippocampal DG zones roughly equally. All proved about equally effective in increasing the levels of NMDAR1, pAMPAR1 and pCaMKII and increasing the Bcl-2/Bax ratio to protect neurons from apoptosis.Conclusion: Exercise induced by electrical stimulation has beneficial effects comparable to those of other types of exercise for alleviating the cognitive deficits of vascular dementia.