Efecto de la tributirina sobre la memoria espacial, la transmisión glutamatérgica hipocampal y la plasticidad sináptica

Abstract

Butyric acid, a short chain fatty acid derived from the intestinal fermentation of dietary fiber, is gaining interest in relation to their possible beneficial effects on neuropsychological disorders. C57BL/6J male mice were used to investigate the effect of tributyrin, a prodrug of butyric acid, on hippocampus-dependent spatial memory, hippocampal synaptic transmission and plasticity mechanisms, and the expression of genes and proteins relevant to hippocampal glutamatergic transmission. We found that free-feeding intake during 48 h of a diet containing 1% tributyrin prevented, in adolescent but not in adult mice, scopolamine-induced impairment of hippocampus-dependent spatial memory. Moreover, tributyrin treatment up-regulated, within the adolescent hippocampus, gene expression of glutamate receptors subunits. On the other hand, in vitro studies carried out in hippocampal slices, revealed that tributyrin is able to transform early-LTP into late-LTP and to rescue LTP-inhibition induced by other molecules such as scopolamine and anandamide and that induced by high saturated fat diet. The facilitation of late-LTP induced by tributyrin was blocked by a PPARγ and AMPK inhibitors, suggesting the involvement of both PPARγ and AMPK on tributyrin effects. In conclusion, the study of tributyrin carried out in this work suggests that this prodrug has a positive influence on LTP and hippocampal-dependent spatial memory, which suggests that butyric acid may have beneficial effects on memory