Effect of deep brain stimulation for lateral hypothalamic area on memory decline and hippocampal neurofilaments expression dysfunctions in aged rats

Abstract

OBJECTIVE: Studying the effect of deep brain stimulation (DBS) in the lateral hypothalamic area (LHA) in young and aging rats regarding memory changes, hippocampal neuronal dystrophy, and neurofilament expression. METHODS: Thirty-six male Sprague-Dawley rats were divided into two main groups: adult young ( n = 18, 8 weeks old) and aged ( n = 18, 24 months old). Each main group was further subdivided into three equal subgroups ( n = 6) including control, sham, and DBS. DBS of LHA was conducted using high-frequency electric currents (130 Hz) for 1.5 h with 5-min breaks every 30 min for five consecutive days. Assessment of working memory was done using passive avoidance test (PAT). Then, the brain was dissected and hippocampal neuronal dystrophic damage was assessed as well as immunohistochemical examination of neurofilaments (NF68, NF200) expression. RESULTS: Aging rats had progressive hippocampal neuronal degeneration and downregulation of heavy and light chain neurofilaments, that was associated with progressive decline in working memory. Nevertheless, activation of DBS in the LHA enhanced memory function as it increased latency to entry in PAT ( P < 0.001) compared to old normal and sham groups. Dystrophic damage score significantly decreased with DBS ( P < 0.001) in the hippocampal CA1, CA3, and dentate gyrus regions. Moreover, DBS upregulated hippocampal NF68, NF200 expression ( P < 0.001) in both young and old rats. We also found a significant positive correlation between working memory and NFs expression and a negative correlation between dystrophic damage score and NFs expression. CONCLUSIONS: DBS in the LHA may have a neuroprotective effect in aging rats as it enhanced the working memory and decreased hippocampal neuronal dystrophy. This protective effect may be caused by the upregulation of neurofilaments.