title: 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 (APPSDLmice). DMSO treatment increased spine density in a region-specific manner in the hippocampus of APPSDLmice 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 Aβ levels, the drug did not exert its function via decreasing the oligomeric Aβ 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 Aβ-mediated synaptotoxicity and behavioral impairment.
authors: Department of Neurobiology, University of Osnabrück, Osnabrück, Germany.
authors: Lorène
authors: L
authors: Penazzi
authors: Department of Neurobiology, University of Osnabrück, Osnabrück, Germany.
authors: Julia
authors: J
authors: Lorengel
authors: Department of Neurobiology, University of Osnabrück, Osnabrück, Germany.
authors: Frederik
authors: F
authors: Sündermann
authors: Department of Neurobiology, University of Osnabrück, Osnabrück, Germany.
authors: Nataliya
authors: N
authors: Golovyashkina
authors: Department of Neurobiology, University of Osnabrück, Osnabrück, Germany.
authors: Stefan
authors: S
authors: Marre
authors: CNRS UMR 7364, Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Université de Strasbourg, UMR 7364, Strasbourg, France.
authors: Chantal M B
authors: CMB
authors: Mathis
authors: Department of Behavioral Biology, University of Osnabrück, Osnabrück, Germany.
authors: Lars
authors: L
authors: Lewejohann
authors: Department of Neurobiology, University of Osnabrück, Osnabrück, Germany.
authors: Roland
authors: R
authors: Brandt
authors: Department of Neurobiology, University of Osnabrück, Osnabrück, Germany. Electronic address: bakota@biologie.uni-osnabrueck.de.
authors: Lidia
authors: L
authors: Bakota
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000818:Animals; D049229:Dendritic Spines / Q000187:drug effects* / Q000473:pathology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology
chemical_list: D016166:Free Radical Scavengers; D004121:Dimethyl Sulfoxide
keywords: Anxiety; Aβ; DMSO; Odor habituation; Spatial memory; Spines