Sleep deprivation increases serotonin 2a receptor response in brain
Environmental stressor alters receptor involved in response to
psychedelic drugs and schizophrenia in a matter of hours.

Date:
January 11, 2022
Source:
University of Arizona Health Sciences
Summary:
Researchers have identified the effects of an environmental
stressor, sleep deprivation, that could alter the balance controlled
by antipsychotic drugs and impact individuals with schizophrenia.



FULL STORY ==========================================================================
The serotonin 2A (5-HT2A) receptor is widely distributed in the brain
and plays a critical role in perception, cognition and psychosis. It is
also responsible for the psychedelic effects of drugs, such as psilocybin (hallucinogenic mushrooms) and LSD. Abnormal 5-HT2A receptor function
is associated with psychiatric disorders, including schizophrenia. The
leading class of antipsychotic drugs used to treat schizophrenia targets
5-HT2A receptors to reduce symptoms of hallucinations and impaired
cognition.


==========================================================================
A study led by Amelia Gallitano, MD, PhD, professor in the Department
of Basic Medical Sciences and Psychiatry at the University of Arizona
College of Medicine -- Phoenix, found that an environmental stressor,
sleep deprivation, can significantly increase the levels of serotonin
2A neurotransmitter receptors in 6 to 8 hoursin animal models. For
individuals with schizophrenia, these findings suggest environmental
stressors may alter the balance in brain receptors that are controlled
by antipsychotic drugs.

"Our study shows it is possible for environmental stimuli to change
the levels of receptors that have important roles in the brain -- in
a matter of hours," said Gallitano, whose labfocuses on investigating
the interaction of environmental stress and genetic predisposition in
the development of psychiatric illnesses. "Now we think we know the
mechanism through which this happens; it's through the gene EGR3.

Signaling Mechanism The role of 5-HT2A receptors in controlling one's
ability to understand and process information has been extensively
studied. However, the signaling process that regulates this gene
expression has remained poorly understood - until now.

Receptor proteins on the surface of brain cells control the internal communication network of the brain. These receptors are created when
a gene (a region of DNA) is turned on and produces the instructions
(messenger RNA) that the cell uses to create the protein, in this case
the 5-HT2A receptor. How many of the receptors are made, and present
on the cell surface, determines how the brain cell responds to the neurotransmitter serotonin, and also to drugs that bind to the receptor,
such as antipsychotics, LSD and psilocybin.



==========================================================================
The 5-HT2A receptor receives its encoded instruction from the HTR2A
gene. The study revealed that proteins produced by EGR3, an early growth response gene, also were required for expression of the 5-HT2A receptor.

The function of EGR3 is to bind to DNA and turn on and off other
genes. The findings showed stimuli caused by sleep deprivation triggered
EGR3 to bind to the 5-HT2A receptor gene and turn on its production of
mRNA instructions to make more protein. This resulted in more 5-HT2A
receptors present in the brain within several hours.

Consequences for Schizophrenia The findings from this study enhance understanding of how environment alters expression of brain receptors
that mediate prefrontal cortex function. Activity in the prefrontal
cortex region of the brain is essential for spatial reasoning and working memory. Dysfunction in this area may contribute to the cognitive deficits
that characterize schizophrenia.

Schizophrenia is a mental illness characterized by abnormalities in
perception, thinking and memory. The illness disrupts cognition, sleep
and memory processes, causing patients to experience hallucinations and disassociation from reality.

In the search for treatments for severe psychiatric symptoms, drugs
that initiate a physiological response by binding to 5-HT2A receptors
are experiencing a resurgence. The fact that 5-HT2A receptors mediate
the hallucinogenic effects of drugs, such as LSD and psilocybin, suggests
this receptor may influence the hallucinations and perceptual disturbances
of schizophrenia.

"We want to understand the genes that get expressed as a result
of environmental stimuli and how that gene-environment interaction
influences behavioral changes that can give rise to mental illness
symptoms," Gallitano said.

This research was supported by National Institutes of Health grants R01 MH097803 and R21 MH113154-01A1 awarded to Gallitano. The findings were published in Molecular Psychiatry.

special promotion Explore the latest scientific research on sleep and
dreams in this free online course from New Scientist -- Sign_up_now_>>> academy.newscientist.com/courses/science-of-sleep-and-dreams ========================================================================== Story Source: Materials provided by
University_of_Arizona_Health_Sciences. Original written by Beth
Smith. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Xiuli Zhao, Annika B. Ozols, Kimberly T. Meyers, Janet Campbell,
Andrew
McBride, Ketan K. Marballi, Amanda M. Maple, Carren Raskin, Abhinav
Mishra, Serena M. Noss, Kelsey L. Beck, Rami Khoshaba, Amulya
Bhaskara, Meghna N. Godbole, James R. Lish, Paul Kang, Chengcheng
Hu, Mikael Palner, Agnete Overgaard, Gitte M. Knudsen, Amelia
L. Gallitano. Acute sleep deprivation upregulates serotonin 2A
receptors in the frontal cortex of mice via the immediate early gene
Egr3. Molecular Psychiatry, 2022; DOI: 10.1038/s41380-021-01390-w ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220111100012.htm

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