Bexarotene therapy ameliorates behavioral deficits and induces functional and molecular changes in very-old Triple Transgenic Mice model of Alzheimer´s disease


Autoři: Jonathan Mauricio Muñoz-Cabrera aff001;  Adrián Gabriel Sandoval-Hernández aff002;  Andrea Niño aff002;  Tatiana Báez aff002;  Angie Bustos-Rangel aff002;  Gloria Patricia Cardona-Gómez aff003;  Alejandro Múnera aff001;  Gonzalo Arboleda aff002
Působiště autorů: Behavioral Neurophysiology Laboratory, School of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia aff001;  Grupo de Muerte Celular, Instituto de Genética, Universidad Nacional de Colombia, Bogotá, Colombia aff002;  Área de Neurobiología Celular y Molecular, Grupo de Neurociencias de Antioquia, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223578

Souhrn

Introduction

Bexarotene, a retinoid X receptor agonist, improves cognition in murine models of Alzheimer’s disease (AD). This study evaluated the effects of bexarotene on pathological and electrophysiological changes in very old triple transgenic AD mice (3xTg-AD mice).

Methods

24-month-old 3xTg-AD mice were treated with bexarotene (100 mg/kg/day for 30 days). The Morris water maze was used to evaluate spatial memory; immunofluorescence and confocal microscopy were used to evaluate pathological changes; and in vivo electrophysiological recordings were used to evaluate basal transmission and plasticity in the commissural CA3-CA1 pathway.

Results

In addition to cognitive improvement, bexarotene-treated 3xTg-AD mice were found to have 1) reductions of astrogliosis and reactive microglia both in cortex and hippocampus; 2) increased ApoE expression restricted to CA1; 3) increased number of cells co-labeled with ApoE and NeuN; 4) recovery of NeuN expression, suggesting neuronal protection; and, 5) recovery of basal synaptic transmission and synaptic plasticity.

Discussion

These results indicate that bexarotene-induced improvement in cognition is due to multiple changes that contribute to recovery of synaptic plasticity.

Klíčová slova:

Alzheimer's disease – Cognitive impairment – Hippocampus – Immunofluorescence – Learning – Mouse models – Quantitative analysis – Synaptic plasticity


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