Title
Amitriptyline-mediated cognitive enhancement in aged 3xTg Alzheimer's disease mice is associated with neurogenesis and neurotrophic activity Amitriptyline-mediated cognitive enhancement in aged 3xTg Alzheimer's disease mice is associated with neurogenesis and neurotrophic activity
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Subject
Engineering sciences. Technology
Source (journal)
PLoS ONE
Volume/pages
6(2011) :6 , 13 p.
ISSN
1932-6203
1932-6203
Article Reference
e21660
Carrier
E-only publicatie
Target language
English (eng)
Full text (Publishers DOI)
Abstract
Approximately 35 million people worldwide suffer from Alzheimer's disease (AD). Existing therapeutics, while moderately effective, are currently unable to stem the widespread rise in AD prevalence. AD is associated with an increase in amyloid beta (A beta) oligomers and hyperphosphorylated tau, along with cognitive impairment and neurodegeneration. Several antidepressants have shown promise in improving cognition and alleviating oxidative stress in AD but have failed as long-term therapeutics. In this study, amitriptyline, an FDA-approved tricyclic antidepressant, was administered orally to aged and cognitively impaired transgenic AD mice (3xTgAD). After amitriptyline treatment, cognitive behavior testing demonstrated that there was a significant improvement in both long-and short-term memory retention. Amitriptyline treatment also caused a significant potentiation of non-toxic A beta monomer with a concomitant decrease in cytotoxic dimer A beta load, compared to vehicle-treated 3xTgAD controls. In addition, amitriptyline administration caused a significant increase in dentate gyrus neurogenesis as well as increases in expression of neurosynaptic marker proteins. Amitriptyline treatment resulted in increases in hippocampal brain-derived neurotrophic factor protein as well as increased tyrosine phosphorylation of its cognate receptor (TrkB). These results indicate that amitriptyline has significant beneficial actions in aged and damaged AD brains and that it shows promise as a tolerable novel therapeutic for the treatment of AD.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/00ef46/8945.pdf
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