Bexarotene-Activated Retinoid X Receptors Regulate Neuronal Differentiation and Dendritic Complexity.
Anais MounierDanko D GeorgievKyong Nyon NamNicholas F FitzEmilie L CastranioCody M WolfeAndrea A CronicanJonathan SchugIliya LefterovRadosveta KoldamovaPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2015)
Bexarotene-activated retinoid X receptors (RXRs) ameliorate memory deficits in Alzheimer's disease mouse models, including mice expressing human apolipoprotein E (APOE) isoforms. The goal of this study was to gain further insight into molecular mechanisms whereby ligand-activated RXR can affect or restore cognitive functions. We used an unbiased approach to discover genome-wide changes in RXR cistrome (ChIP-Seq) and gene expression profile (RNA-Seq) in response to bexarotene in the cortex of APOE4 mice. Functional categories enriched in both datasets revealed that liganded RXR affected signaling pathways associated with neurogenesis and neuron projection development. The significance of RXR for these functions was validated in mouse embryonic stem cells, primary neurons, and APOE3 and APOE4 mice treated with bexarotene.
Keyphrases
- rna seq
- cognitive decline
- single cell
- genome wide
- high fat diet
- high fat diet induced
- embryonic stem cells
- mild cognitive impairment
- dna methylation
- signaling pathway
- high throughput
- mouse model
- insulin resistance
- traumatic brain injury
- copy number
- magnetic resonance imaging
- spinal cord
- metabolic syndrome
- computed tomography
- skeletal muscle
- functional connectivity
- blood brain barrier
- pi k akt
- induced apoptosis