DMSO modulates CNS function in a preclinical Alzheimer's disease model

Abstract

DMSO has a widespread use as a vehicle for water-insoluble therapeutic drug candidates but may also exert disease-relevant pharmacological effects by itself. However, its influence on the CNS has hardly been addressed. Here we examined the brain structure and function following chronic exposure to low DMSO dose at a paradigm with flawed synaptic connectivity in a preclinical transgenic mouse model for Alzheimer's disease (APP(SDL) mice). DMSO treatment increased spine density in a region-specific manner in the hippocampus of APP(SDL) mice ex vivo and in vivo. Moreover, DMSO exhibited clear influence on the behavior of this mouse line by enhancing hippocampal-dependent spatial memory accuracy, modulating hippocampal-independent olfactory habituation and displaying anxiolytic effect. Despite that most of the action of DMSO was observed in animals with elevated All levels, the drug did not exert its function via decreasing the oligomeric A beta species. However, challenging organotypic hippocampal slice cultures with NMDA receptor antagonist MK-801 recapitulated the effect of DMSO on spine density, indicating a tuning influence of DMSO on receptor signalization. Our findings demonstrate that DMSO should be considered as a true bioactive compound, which has the potential to be a beneficial adjuvant to counteract A beta mediated synaptotoxicity and behavioral impairment. (C) 2016 The Authors. Published by Elsevier Ltd.