title: Mildronate improves cognition and reduces amyloid-β pathology in transgenic Alzheimer's disease mice.
abstract: Mildronate, a carnitine congener drug, previously has been shown to provide neuroprotection in an azidothymidine-induced mouse model of neurotoxicity and in a Parkinson's disease rat model. The aim of this study was to investigate the effects of mildronate treatment on cognition and pathology in Alzheimer's disease (AD) model mice (APP(SweDI)). Mildronate was administered i.p. daily at 50 or 100 mg/kg for 28 days. At the end of treatment, the animals were behaviorally and cognitively tested, and brains were assessed for AD-related pathology, inflammation, synaptic markers, and acetylcholinesterase (AChE). The data show that mildronate treatment significantly improved animal performance in water maze and social recognition tests, lowered amyloid-β deposition in the hippocampus, increased expression of the microglia marker Iba-1, and decreased AChE staining, although it did not alter expression of proteins involved in synaptic plasticity (GAP-43, synaptophysin, and GAD67). Taken together, these findings indicate mildronate's ability to improve cognition and reduce amyloid-β pathology in a mouse model of AD and its possible therapeutic utility as a disease-modifying drug in AD patients.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Latvia, Riga, Latvia.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Beitnere
authors.forename: Thomas
authors.initials: T
authors.lastname: van Groen
authors.forename: Ashish
authors.initials: A
authors.lastname: Kumar
authors.forename: Baiba
authors.initials: B
authors.lastname: Jansone
authors.forename: Vija
authors.initials: V
authors.lastname: Klusa
authors.forename: Inga
authors.initials: I
authors.lastname: Kadish
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D008124:Locomotion / Q000187:drug effects / Q000235:genetics; D008763:Methylhydrazines / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D012919:Social Behavior
chemical_list: D000276:Adjuvants, Immunologic; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein; D008763:Methylhydrazines; C050147:3-(2,2,2-trimethylhydrazine)propionate; D000110:Acetylcholinesterase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
keywords: Alzheimer's disease; cognition; hippocampus; mildronate; transgenic mice