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

Autor(en): Penazzi, Lorène
Lorengel, Julia
Sündermann, Frederik
Golovyashkina, Nataliya
Marre, Stefan
Mathis, Chantal M. B.
Lewejohann, Lars 
Brandt, Roland 
Bakota, Lidia
Affiliationen: Department of Neurobiology, University of Osnabrück, Osnabrück, Germany. Department of Neurobiology, University of Osnabrück, Osnabrück, Germany. Department of Neurobiology, University of Osnabrück, Osnabrück, Germany. Department of Neurobiology, University of Osnabrück, Osnabrück, Germany. Department of Neurobiology, University of Osnabrück, Osnabrück, Germany. CNRS UMR 7364, Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Université de Strasbourg, UMR 7364, Strasbourg, France. Department of Behavioral Biology, University of Osnabrück, Osnabrück, Germany. Department of Neurobiology, University of Osnabrück, Osnabrück, Germany. Department of Neurobiology, University of Osnabrück, Osnabrück, Germany. Electronic address: bakota@biologie.uni-osnabrueck.de.
Erscheinungsdatum: 2017
Journal: Neuropharmacology
Volumen: 113
Ausgabe: Pt A
Startseite: 434
Seitenende: 444
Zusammenfassung: 
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 (APPSDL mice). DMSO treatment increased spine density in a region-specific manner in the hippocampus of APPSDL 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 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.
DOI: 10.1016/j.neuropharm.2016.10.020

Show full item record

Page view(s)

2
Last Week
0
Last month
0
checked on Apr 16, 2024

Google ScholarTM

Check

Altmetric