Medial septum deep brain stimulation enhances memory and hippocampal neurogenesis in the D-galactose induced rat model of aging: behavioral and immunohistochemical study.

Abstract

One of the cardinal features of aging is brain aging, which manifests itself in impaired cognitive functions. Experimental data suggest that deep brain stimulation (DBS) can improve memory functions when stimulating specific brain regions. In present study we tested the hypothesis that medial septum (MS) DBS enhances memory function by modulating the hippocampal neurogenesis in the D-galactose (D-gal) induced rat model of aging. Rats were randomly assigned to four experimental groups: (1) control, (2) administration of D-gal, (3) administration of D-gal and electrode implantation and (4) administration of D-gal, electrode implantation and stimulation. Our results showed that MS DBS significantly enhanced the memory functions in an animal model of aging induced by D-gal administration, which impaired long-term spatial memory in the Morris water maze and impaired spatial and object novelty recognition memory in the open field. The immunohistochemical studies showed that in the Dentate Gyrus (DG) of rats with D-gal administration or D-gal combined with electrode implantation, the number of NeuN (neuronal nuclear antigen) or Doublecortin-immunopositive cells decreased (Doublecortin - a biomarker for the post-mitotic phase of cells); MS stimulation increases the number of these cells in the DG to levels comparable to the control group. Thus, MS-DBS restores the level of hippocampal neurogenesis. The present data demonstrate for the first time that chronic DBS of the MS restores memory functions in a D-gal-induced animal model of aging, and that one of the important underlying mechanisms is mediated by enhanced neurogenesis in the hippocampus.