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Therapeutic and preventive effects of methylene blue on Alzheimer's disease pathology in a transgenic mouse model.
Neuropharmacology. 2014 Jan; 76 Pt A:68-79.N

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+Show Affiliations

Aix-Marseille Université, UMR 7260, FR3C, Lab. Neurosciences Intégratives et Adaptatives, 13331 Marseille, France. Electronic address: veronique.paban@univ-amu.fr.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23891615

Citation

Paban, V, et al. "Therapeutic and Preventive Effects of Methylene Blue On Alzheimer's Disease Pathology in a Transgenic Mouse Model." Neuropharmacology, vol. 76 Pt A, 2014, pp. 68-79.
Paban V, Manrique C, Filali M, et al. Therapeutic and preventive effects of methylene blue on Alzheimer's disease pathology in a transgenic mouse model. Neuropharmacology. 2014;76 Pt A:68-79.
Paban, V., Manrique, C., Filali, M., Maunoir-Regimbal, S., Fauvelle, F., & Alescio-Lautier, B. (2014). Therapeutic and preventive effects of methylene blue on Alzheimer's disease pathology in a transgenic mouse model. Neuropharmacology, 76 Pt A, 68-79. https://doi.org/10.1016/j.neuropharm.2013.06.033
Paban V, et al. Therapeutic and Preventive Effects of Methylene Blue On Alzheimer's Disease Pathology in a Transgenic Mouse Model. Neuropharmacology. 2014;76 Pt A:68-79. PubMed PMID: 23891615.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Therapeutic and preventive effects of methylene blue on Alzheimer's disease pathology in a transgenic mouse model. AU - Paban,V, AU - Manrique,C, AU - Filali,M, AU - Maunoir-Regimbal,S, AU - Fauvelle,F, AU - Alescio-Lautier,B, Y1 - 2013/07/23/ PY - 2013/02/21/received PY - 2013/05/14/revised PY - 2013/06/19/accepted PY - 2013/7/30/entrez PY - 2013/7/31/pubmed PY - 2014/6/6/medline KW - APP/PS1 mice KW - Beta-amyloid KW - Cortex KW - HRMAS NMR KW - Hippocampus KW - Memory KW - jMRUI SP - 68 EP - 79 JF - Neuropharmacology JO - Neuropharmacology VL - 76 Pt A N2 - 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'. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/23891615/Therapeutic_and_preventive_effects_of_methylene_blue_on_Alzheimer's_disease_pathology_in_a_transgenic_mouse_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(13)00318-3 DB - PRIME DP - Unbound Medicine ER -