Activation of LXR β Signaling in the Amygdala Confers Anxiolytic Effects Through Rebalancing Excitatory and Inhibitory Neurotransmission upon Acute Stress

In this study, we found stress-induced anxiety led to the expression reduction of LXRβ not LXRα in mice amygdala. GW3965, a dual agonist for both LXRα and LXRβ, alleviated anxiety-like behaviors of stressed mice through activation of LXRβ, confirmed by the knockdown of LXRβ m ediated by lentiviral shRNAs in the basolateral amygdala (BLA). This was paralleled by correcting the disequilibrium of E/I neurotransmission in the stressed BLA. Importantly, GW3965 exerted anxiolytic effects by correcting the promoted amplitude and frequency of miniature excitatory postsynaptic cu rrent (mEPSC), and augmenting the decreased that of miniature inhibitory postsynaptic current (mIPSC) in the stressed BLA. This suggests that stress-induced anxiety-like behaviors can largely be ascribed to the deficit of LXRβ signaling in E/I neurotransmission in BLA. These findings highlight the deficiency of LXRβ signaling in the amygdala linked to anxiety disorder, and LXRβ activation may represent a potential novel target for anxiety treatment with an alteration in synaptic transmission in the amygdala.

Source: Neurotherapeutics - April 14, 2020 Category: Neurology Source Type: research