Rescuing Effects of RXR Agonist Bexarotene on Aging-related Synapse Loss Depend on Neuronal LRP1.

Rescuing Effects of RXR Agonist Bexarotene on Aging-related Synapse Loss Depend on Neuronal LRP1. Exp Neurol. 2015 Dec 11; Authors: Tachibana M, Shinohara M, Yamazaki Y, Liu CC, Rogers J, Bu G, Kanekiyo T Abstract Apolipoprotein E (apoE) plays a critical role in maintaining synaptic integrity by transporting cholesterol to neurons through the low-density lipoprotein receptor related protein-1 (LRP1). Bexarotene, a retinoid X receptor (RXR) agonist, has been reported to have potential beneficial effects on cognition by increasing brain apoE levels and lipidation. To investigate the effects of bexarotene on aging-related synapse loss and the contribution of neuronal LRP1 to the pathway, forebrain neuron-specific LRP1 knockout (nLrp1(-/-)) and littermate control mice were administered with bexarotene-formulated diet (100mg/kg/day) or control diet at the age of 20-24months for 8weeks. Upon bexarotene treatment, levels of brain apoE and ATP-binding cassette sub-family A member 1 (ABCA1) were significantly increased in both mice. While levels of PSD95, glutamate receptor 1 (GluR1), and N-methyl-D-aspartate receptor NR1 subunit (NR1), which are key postsynaptic proteins that regulate synaptic plasticity, were decreased with aging, they were restored by bexarotene treatment in the brains of control but not nLrp1(-/-) mice. These results indicate that the beneficial effects of bexarotene on synaptic integrity depend on the presence of neurona...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research