Butyric Acid Precursor Tributyrin Modulates Hippocampal Synaptic Plasticity and Prevents Spatial Memory Deficits: Role of PPARγ and AMPK

Abstract

Background Short chain fatty acids (SCFA), such as butyric acid (BA), derived from the intestinal fermentation of dietary fiber and contained in dairy products, are gaining interest in relation to their possible beneficial effects on neuropsychological disorders Methods C57BL/6J male mice were used to investigate the effect of tributyrin (TB), a prodrug of BA, on hippocampus (HIP)-dependent spatial memory, HIP synaptic transmission and plasticity mechanisms, and the expression of genes and proteins relevant to HIP glutamatergic transmission. Results Ex vivo studies, carried out in HIP slices, revealed that TB is able to transform early-LTP (e-LTP) into late-LTP (l-LTP) and to rescue LTP-inhibition induced by scopolamine (SCOP). The facilitation of l-LTP induced by TB was blocked both by GW9662 (a PPARγ antagonist) and C-Compound (an AMPK inhibitor), suggesting the involvement of both PPARγ and AMPK on TB effects. Moreover, 48-hour intake of a diet containing 1% TB prevented, in adolescent but not in adult mice, SCOP-induced impairment of HIP-dependent spatial memory. In the adolescent HIP, TB up-regulated gene expression levels of Pparg, leptin and adiponectin receptors, and that of the glutamate (GLU) receptor subunits AMPA-2, NMDA-1, NMDA-2A and NMDA-2B. Conclusions Our study shows that TB has a positive influence on LTP and HIP-dependent spatial memory, which suggests that BA may have beneficial effects on memory.

Tributyrin displayed the potential nutrient mechanism by improving the growth of rumen bacteria of weaned lambs rather than via releasing butyric acid

“…For a long time, TB was regarded as a precursor of butyric acid [7,20,21] since early several in vitro studies on different cancer cell lines showed that TB can induce apoptosis at millmolar levels. Accordingly, Watkins et al…”

Impact of gut microbiota and associated mechanisms on postprandial glucose levels in patients with diabetes

“…[ 61 ] SCFAs are organic fatty acids that contain 1–6 carbon atoms. [ 62 ] Butyrate is the main energy source for gut epithelial cells, [ 63 ] and is closely associated with metabolism. SCFAs also include formic, acetic, and propionic acids.…”