Medeiros_2014_Am.J.Pathol_184_520

Reference

Title : alpha7 Nicotinic Receptor Agonist Enhances Cognition in Aged 3xTg-AD Mice with Robust Plaques and Tangles - Medeiros_2014_Am.J.Pathol_184_520
Author(s) : Medeiros R , Castello NA , Cheng D , Kitazawa M , Baglietto-Vargas D , Green KN , Esbenshade TA , Bitner RS , Decker MW , LaFerla FM
Ref : American Journal of Pathology , 184 :520 , 2014
Abstract :

Alzheimer disease (AD) is a progressive neurodegenerative disorder with associated memory loss, spatial disorientation, and other psychiatric problems. Cholinergic system dysfunction is an early and salient feature of AD, and enhancing cholinergic signaling with acetylcholinesterase inhibitors is currently the primary strategy for improving cognition. The beneficial effects of acetylcholinesterase inhibitors, however, are typically short-lived and accompanied by adverse effects. Recent evidence suggests that activating alpha7 nicotinic acetylcholine receptors (alpha7 nAChR) may facilitate the specific modulation of brain cholinergic signaling, leading to cognitive enhancement and possibly to amelioration of AD pathologic findings. In the present study, we determined the effect of long-term treatment with the selective alpha7 nAChR agonist A-582941 in aged 3xTg-AD mice with robust AD-like pathology, which is particularly significant not only because this is the only mouse model that co-develops amyloid plaques and neurofibrillary tangles but also because it enabled us to explore whether A-582941 is able to restore brain function after the severe damage associated with AD. Analysis of beta-amyloid deposits, tau phosphorylation, and inflammatory cells revealed that, overall, pathologic findings were unchanged. Rather, alpha7 nAChR activation induced expression of c-Fos and brain-derived neurotrophic factor and phosphorylation of cyclic adenosine monophosphate response element binding and neurotrophic tyrosine receptor kinase type 2. More important, A-582941 completely restored cognition in aged 3xTg-AD mice to the level of that in age-matched nontransgenic mice. These novel findings indicate that activating alpha7 nAChR is a promising treatment for cognitive impairment in AD.

PubMedSearch : Medeiros_2014_Am.J.Pathol_184_520
PubMedID: 24269557

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Citations formats

Medeiros R, Castello NA, Cheng D, Kitazawa M, Baglietto-Vargas D, Green KN, Esbenshade TA, Bitner RS, Decker MW, LaFerla FM (2014)
alpha7 Nicotinic Receptor Agonist Enhances Cognition in Aged 3xTg-AD Mice with Robust Plaques and Tangles
American Journal of Pathology 184 :520

Medeiros R, Castello NA, Cheng D, Kitazawa M, Baglietto-Vargas D, Green KN, Esbenshade TA, Bitner RS, Decker MW, LaFerla FM (2014)
American Journal of Pathology 184 :520