The antidepressant-like effect of chronic guanosine treatment is associated with increased hippocampal neuronal differentiation

Abstract

Guanosine is a purine nucleoside that occurs naturally in the central nervous system, exerting trophic effects. Given its neuroprotective properties, the potential of guanosine as an antidepressant has been recently examined. Within this context, the present study sought to investigate the effects of chronic treatment with guanosine on the tail suspension test (TST), open field test and adult hippocampal neurogenesis. Swiss mice were administered guanosine for 21 days (5 mg/kg/day, p.o.) and subsequently submitted to the TST and open-field test. Following behavioural testing, animals were killed and the brains were processed for immunohistochemical analyses of hippocampal cell proliferation and neuronal differentiation. Animals treated with guanosine showed a reduction in immobility time in the TST without alterations in locomotor activity, confirming the antidepressant-like effect of this compound. Quantitative microscopic analysis did not reveal significant alterations in the numbers of Ki-67- and proliferating cell nuclear antigen (PCNA)-positive cells in the hippocampal dentate gyrus (DG) of guanosine-treated mice. However, guanosine treatment resulted in a significant increase in the number of immature neurons, as assessed by immunohistochemistry for the neurogenic differentiation protein. Interestingly, this effect was localized to the ventral hippocampal DG, a functionally distinct region of this structure known to regulate emotional and motivational behaviours. Taken together, our results suggest that the antidepressant-like effect of chronic guanosine treatment is associated with an increase in neuronal differentiation, reinforcing the notion that this nucleoside may be an endogenous mood modulator.

Keywords: antidepressant; dentate gyrus; hippocampus; mouse; tail suspension test.