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

丁酸前体三丁酸甘油酯调节海马突触可塑性并预防空间记忆缺陷:PPARγ 和 AMPK 的作用

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作者:Ana Belén Sanz-Martos, Jesús Fernández-Felipe, Beatriz Merino, Victoria Cano, Mariano Ruiz-Gayo, Nuria Del Olmo

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.

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.

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 can transform early-LTP into late-LTP (l-LTP) and to rescue LTP-inhibition induced by scopolamine. 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, scopolamine-induced impairment of HIP-dependent spatial memory. In the adolescent HIP, TB upregulated gene expression levels of Pparg, leptin, and adiponectin receptors, and that of the glutamate 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.

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