Deficient Memory, Long-Term Potentiation and Hippocampal Synaptic Plasticity in Galectin-4-KO Mice

Abstract

Intestinal infections trigger inflammation and can contribute to degenerative and cognitive brain pathologies through the microbiota-gut-brain axis. Galectin-4 is an intestinal lectin key in the control of pathogenic bacterial infections. Here we report that galectin-4 deficient mice (Lgals4-KO) show an altered intestinal commensal microbiota in the absence of pathogens, defining a new role of galectin-4 in the modulation of commensal bacteria. Strikingly, Lgals4-KO mice present a deficient memory formation, and impaired hippocampal long-term potentiation (LTP) in vivo and ex vivo. Furthermore, Lgals4-KO neurons show a reduced activation of the AMPA receptor and of the CaMKII upon chemically induced LTP in vitro. These mice also display significantly lower dendritic spine density and shorter spine length in hippocampal dendrites, as well as an increased area of the postsynaptic densities, all coherent with an alteration of the synaptic function. In all, our results demonstrate that the absence of galectin-4 induces synaptic dysfunctions and memory impairment, along with changes in gut microbial composition, suggesting that variations in endogenous intestinal microbiota may cause or contribute to such neurological pathologies.