Abstract
Background Deep brain stimulation (DBS) provides substantial clinical benefits for a variety of movement disorders and lately emerged as a potential treatment for cognitive and mood disorders. Regulation of adult hippocampal neurogenesis may play a chief role in mediating DBS effects. Nevertheless, there exist significant sex differences in the regulation of neurogenesis influenced mainly by gonadal hormone exposure. Objective To investigate the hippocampal neurogenic differences between male and female awake and unrestrained rats in response to unilateral anteromedial thalamic nucleus (AMN) stimulation. Methods Four groups of adult Sprague-Dawley male and female rats received unilateral stimulation ( n = 6 each) or sham surgery of electrode implantation with no current delivery ( n = 4 each) in the right AMN; A naive group of males and females ( n = 4 each) was also included. Rats received 4 injections (50 mg/Kg/injection) of 5′-bromo-2′-deoxyuridine (BrdU) 3 days post-surgery and were euthanized 24h later. The fractionator method was used together with confocal immunofluorescent analysis to probe for BrdU-, GFAP- and NeuN-positive cells in the dentate gyrus (DG). Results Focal neurogenesis was induced in the ipsilateral DG after AMN stimulation. Stimulation-induced effects were gender-independent and translated into a 76% increase in proliferation of neural stem/progenitor cells. Conclusions Despite the difference in basal neurogenic level between male and female rats, the current study demonstrates that DBS elicits gender-independent neurogenic effects that might have implications in the treatment of cognitive and behavioral disorders irrespective of sex of patients.
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