title: Combination of memantine and vitamin D prevents axon degeneration induced by amyloid-beta and glutamate.
abstract: The currently available drugs for treatment of Alzheimer's disease are symptomatic and only temporarily slow down the natural history of the disease process. Recently, its has been proposed that the combination of memantine with vitamin D, a neurosteroid hormone, may prevent amyloid-beta and glutamate neurotoxicity. Here, our purpose was to examine the potential protective effects of memantine and vitamin D against amyloid-beta peptide and glutamate toxicity in cortical neuronal cultures. We provide the first evidence that cortical axons degenerate less after exposure to amyloid-beta peptide or glutamate in microfluidic neuronal cultures enriched with memantine plus vitamin D compared to control medium and cultures enriched with only memantine or only vitamin D. The reported synergistic neuroprotective effect of memantine plus vitamin D -the combination originating an effect stronger than the sum- corroborate previous clinical finding that Alzheimer's disease patients using this drug combination have improved cognition. This finding reinforces the pharmacological potential of a new drug combining memantine plus vitamin D for the treatment or the prevention of Alzheimer's disease.
authors.affiliation: Department of Neuroscience, Division of Geriatric Medicine, Angers University Hospital, Angers, France; University Memory Clinic, Angers, France; UPRES EA 4638, University of Angers, UNAM, Angers, France; Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and Dentistry, the University of Western Ontario, London, Ontario, Canada. Electronic address: CeAnnweiler@chu-angers.fr.
authors.forename: Cédric
authors.initials: C
authors.lastname: Annweiler
authors.forename: Bernard
authors.initials: B
authors.lastname: Brugg
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Peyrin
authors.forename: Robert
authors.initials: R
authors.lastname: Bartha
authors.forename: Olivier
authors.initials: O
authors.lastname: Beauchet
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D001369:Axons / Q000473:pathology*; D002478:Cells, Cultured; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000633:toxicity*; D008559:Memantine / Q000494:pharmacology* / Q000627:therapeutic use*; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000517:prevention & control*; D018696:Neuroprotective Agents; D014807:Vitamin D / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D016229:Amyloid beta-Peptides; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D014807:Vitamin D; D018698:Glutamic Acid; D008559:Memantine
keywords: Alzheimer's disease; Amyloid-beta; Glutamate; Memantine; Neuroprotection; Vitamin D