Pacemaker in the aged brain: From molecular profiling to memory enhancement

Abstract

Ageing is a major predicting risk factor for dementia and no treatment is currently available for this disorder. Although promising outcome has been reported for electrical stimulation on dementia, the molecular mechanisms still remain obscure. In an aged rat model, our results demonstrate that both entorhinal and perifornical stimulation enhanced spatial memory in the Morris water-maze without affecting anxiety levels. The microarray profiling showed a total of 1514 and 321 coding genes differentially expressed in the hippocampus, with a distinct pattern of signaling mechanisms involving the neurotransmission and neuroplasticity-related functions of entorhinal and perifornical stimulation, respectively. These results were further supported by protein changes associated with neurotransmission and neuroplasticity markers measured by western-blotting, mass-spectrometry, and FACS-based methods. Our present study identified a broad range of molecular pathways involved in the entorhinal and perifornical stimulation-induced memory enhancement, which could potentially be a promising therapeutic strategy for dementia.