Journal article
Neuronally-directed effects of RXR activation in a mouse model of Alzheimer's disease
Scientific reports, Vol.7(1), pp.42270-42270
02/16/2017
DOI: 10.1038/srep42270
PMCID: PMC5311933
PMID: 28205585
Abstract
Alzheimer’s disease (AD) is characterized by extensive neuron loss that accompanies profound impairments in memory and cognition. We examined the neuronally directed effects of the retinoid X receptor agonist bexarotene in an aggressive model of AD. We report that a two week treatment of 3.5 month old 5XFAD mice with bexarotene resulted in the clearance of intraneuronal amyloid deposits. Importantly, neuronal loss was attenuated by 44% in the subiculum in mice 4 months of age and 18% in layer V of the cortex in mice 8 months of age. Moreover, bexarotene treatment improved remote memory stabilization in fear conditioned mice and improved olfactory cross habituation. These improvements in neuron viability and function were correlated with significant increases in the levels of post-synaptic marker PSD95 and the pre-synaptic marker synaptophysin. Moreover, bexarotene pretreatment improved neuron survival in primary 5XFAD neurons in vitro in response to glutamate-induced excitotoxicity. The salutary effects of bexarotene were accompanied by reduced plaque burden, decreased astrogliosis, and suppression of inflammatory gene expression. Collectively, these data provide evidence that bexarotene treatment reduced neuron loss, elevated levels of markers of synaptic integrity that was linked to improved cognition and in an aggressive model of AD.
Details
- Title: Subtitle
- Neuronally-directed effects of RXR activation in a mouse model of Alzheimer's disease
- Creators
- M. M. Mariani - Case Western Reserve UniversityT. Malm - Case Western Reserve UniversityR. Lamb - Case Western Reserve UniversityT. R. Jay - Case Western Reserve UniversityL. Neilson - Case Western Reserve UniversityB. Casali - Case Western Reserve UniversityL. Medarametla - Case Western Reserve UniversityG. E. Landreth - Case Western Reserve University
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.7(1), pp.42270-42270
- DOI
- 10.1038/srep42270
- PMID
- 28205585
- PMCID
- PMC5311933
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Grant note
- 9R56NS084856 / National Institutes of Health F32AG046039 / National Institutes of Health (http://data.elsevier.com/vocabulary/SciValFunders/100000002) National Institutes of Health (http://data.elsevier.com/vocabulary/SciValFunders/100000002) National Institute of Neurological Disorders and Stroke (http://data.elsevier.com/vocabulary/SciValFunders/100000065) R56NS084856 / National Institute of Neurological Disorders and Stroke (http://data.elsevier.com/vocabulary/SciValFunders/100000065)
- Language
- English
- Date published
- 02/16/2017
- Academic Unit
- Neurology
- Record Identifier
- 9985089435002771
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