One study found that environmental stress, and lack of sleep, can significantly increase levels of 2A (5-HT 2A ) neurotransmitter receptors
.
For people with schizophrenia, these findings suggest that environmental stress may alter the balance of brain receptors controlled by antipsychotic drugs
.
"Our study shows that environmental stimuli have the potential to alter the levels of receptors that play important roles in the brain within hours,
" said Galitano, whose lab focuses on studying environmental stress and genetic susceptibility in mental health Interactions in disease development
.
"Now we think we know how this happens; it's through the gene EGR3
.
signaling mechanism
The role of the 5-HT2A receptor in controlling the human ability to understand and process information has been extensively studied
.
However, until now, little was known about the signaling processes that regulate the expression of this gene
.
Receptor proteins on the surface of brain cells control communication networks within the brain
.
These receptors are created when a gene (part of DNA) is turned on and produces instructions (messenger RNA), which the cell uses to make proteins, in this case the 5-HT2A receptor
.
How many receptors are made and appear on the cell surface determines how brain cells respond to the neurotransmitter serotonin, as well as to drugs that bind to the receptors, such as antipsychotics, LSD and psilocybin
.
The 5-HT2A receptor receives encoded instructions from the HTR2A gene
.
The study showed that the protein produced by the early growth response gene EGR3 also requires the expression of the 5-HT2A receptor
.
The function of EGR3 is to bind to DNA and turn other genes on and off
.
The findings suggest that stimulation caused by sleep deprivation triggers EGR3 to bind to the 5-HT2A receptor gene and initiate the production of its mRNA instructions to make more protein
.
This caused more 5-HT2A receptors to appear in the brain within a few hours
.
effects on schizophrenia
The results of this study enhance our understanding of how the environment alters the expression of brain receptors that regulate function in the prefrontal cortex
.
Activity in a region of the brain's prefrontal cortex is critical for spatial reasoning and working memory
.
Dysfunction in this region may contribute to cognitive deficits in schizophrenia
.
Schizophrenia is a mental illness characterized by abnormalities in perception, thinking, and memory
.
The disorder disrupts cognitive, sleep and memory processes, causing patients to hallucinate and disengage from reality
.
Drugs that trigger a physiological response by binding to the 5-HT2A receptor are seeing a resurgence in the search for ways to treat symptoms of severe mental illness
.
The fact that the 5-HT2A receptor mediates the hallucinogenic effects of drugs such as LSD and psilocybin suggests that this receptor may influence hallucinations and perceptual disturbances in schizophrenia
.
"We wanted to understand how genes behave in response to environmental stimuli and how gene-environment interactions influence behavioral changes that can lead to psychiatric symptoms," Garitano said
.
This research was supported by NIH grants R01 MH097803 and R21 MHh113154-01a1 awarded to Galitano
.
The findings were published in the journal Molecular Psychiatry
.
Journal Reference :
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 .
htm (accessed January 11, 2022).
