title: Therapeutic and preventive effects of methylene blue on Alzheimer's disease pathology in a transgenic mouse model.
abstract: Methylene blue (MB) belongs to the phenothiazinium family. It has been used to treat a variety of human conditions and has beneficial effects on the central nervous system in rodents with and without brain alteration. The present study was designed to test whether chronic MB treatment taken after (therapeutic effect) or before (preventive effect) the onset of beta-amyloid pathology influences cognition in a transgenic mouse model (APP/PS1). In addition, the present study aims at revealing whether these behavioral effects might be related to brain alteration in beta-amyloid deposition. To this end, we conducted an in vivo study and compared two routes of drug administration, drinking water versus intraperitoneal injection. Results showed that transgenic mice treated with MB orally or following intraperitoneal injection were protected from cognitive impairments in a variety of social, learning, and exploratory tasks. Immunoreactive beta-amyloid deposition was significantly reduced in the hippocampus and adjacent cortex in MB-treated transgenic mice. Interestingly, these beneficial effects were observed independently of beta-amyloid load at the time of MB treatment. This suggests that MB treatment is beneficial at both therapeutic and preventive levels. Using solid-state High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HRMAS-NMR), we showed that MB administration after the onset of amyloid pathology significantly restored the concentration of two metabolites related to mitochondrial metabolism, namely alanine and lactate. We conclude that MB might be useful for the therapy and prevention of Alzheimer's disease. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.
authors.affiliation: Aix-Marseille Université, UMR 7260, FR3C, Lab. Neurosciences Intégratives et Adaptatives, 13331 Marseille, France. Electronic address: veronique.paban@univ-amu.fr.
authors.forename: V
authors.initials: V
authors.lastname: Paban
authors.forename: C
authors.initials: C
authors.lastname: Manrique
authors.forename: M
authors.initials: M
authors.lastname: Filali
authors.forename: S
authors.initials: S
authors.lastname: Maunoir-Regimbal
authors.forename: F
authors.initials: F
authors.lastname: Fauvelle
authors.forename: B
authors.initials: B
authors.lastname: Alescio-Lautier
mesh_terms: D000284:Administration, Oral; D000409:Alanine / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004192:Discrimination, Psychological / Q000187:drug effects; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008751:Methylene Blue / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009425:Nesting Behavior / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D019344:Lactic Acid; D000409:Alanine; D008751:Methylene Blue
keywords: APP/PS1 mice; Beta-amyloid; Cortex; HRMAS NMR; Hippocampus; Memory; jMRUI