Neuronally-directed effects of RXR activation in a mouse model of Alzheimer's disease
| Autor: | Brad T. Casali, Lee E. Neilson, Taylor R. Jay, Tarja Malm, Gary E. Landreth, L. Medarametla, R. Lamb, Monica M. Mariani |
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| Přispěvatelé: | A.I. Virtanen -instituutti |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Excitotoxicity Hippocampus Plaque Amyloid medicine.disease_cause Amyloid beta-Protein Precursor 0302 clinical medicine Medicine Gliosis Neurons Bexarotene Multidisciplinary biology Olfactory Bulb 3. Good health Astrogliosis medicine.anatomical_structure Cytokines Female Alzheimer's disease medicine.symptom medicine.drug medicine.medical_specialty Tetrahydronaphthalenes Cell Survival Neurotoxins Glutamic Acid Mice Transgenic Article 03 medical and health sciences Alzheimer Disease Memory Internal medicine Animals Habituation Psychophysiologic Inflammation Amyloid beta-Peptides business.industry Membrane Transport Proteins medicine.disease Disease Models Animal Retinoid X Receptors 030104 developmental biology Endocrinology Receptors LDL nervous system Synapses Synaptophysin biology.protein Neuron business Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports |
| Popis: | 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. published version peerReviewed |
| Databáze: | OpenAIRE |
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