Sleep deprivation rapidly upregulates serotonin 2A receptor expression via the immediate early gene Egr3
X. Zhao, K. T. Meyers, A. Mcbride, K. K. Marballi, A. M. Maple, K. L. Beck, P. Kang, Mikael Palner, Agnete Overgaard, Gitte M. Knudsen, A. L. Gallitano
bioRxiv Preprint Server February 23, 2020 preprint DOI: 10.1101/634410 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Mice |
| Intervention | sleep deprivation |
| Duration | 6-8 hours |
| Topics | Serotonin |
| Citations | 1 |
| Key findings | Sleep deprivation upregulates 5-HT2ARs in the mouse frontal cortex via EGR3 binding to the Htr2a promoter. |
Abstract
Serotonin 2A receptors (5-HT2ARs) mediate the effects of hallucinogenic drugs and antipsychotic medications, and are reduced in schizophrenia patients’ brains. However, the mechanisms that regulate 5-HT2AR expression remain poorly understood. We show that an environmental stimulus, sleep deprivation, upregulates 5-HT2ARs in the mouse frontal cortex (FC) in just 6-8 hours. This induction requires the immediate early gene transcription factor early growth response 3 (Egr3). Further, EGR3 binds to the Htr2a promoter in the FC in vivo, and drives reporter construct expression in vitro via two Htr2a promoter binding sites. These findings suggest that EGR3 directly regulates FC Htr2a expression in response to physiologic stimuli, providing a mechanism by which environment rapidly alters levels of a brain receptor that mediates symptoms, and treatment, of mental illness.