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, M. Palner, A. Overgaard, G. M. Knudsen, A. L. Gallitano
bioRxiv Preprint Server February 23, 2020 preprint DOI: 10.1101/634410 via bioRxiv
Summary
Sleep deprivation for 6-8 hours increases serotonin 2A receptors (5-HT2ARs) in the frontal cortex of mice. This upregulation requires the transcription factor early growth response 3 (Egr3), which binds directly to the Htr2a gene's promoter. The finding suggests a mechanism by which environmental stimuli can rapidly alter levels of a brain receptor involved in the effects of hallucinogenic drugs, antipsychotic medications, and schizophrenia.
Study at a glance
| Characteristics | Experimental study |
|---|---|
| Population | Mice |
| Citations | 1 |
| Key finding | 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.