Acute sleep deprivation upregulates serotonin 2A receptors in the frontal cortex of mice via the immediate early gene Egr3

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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

In: Molecular Psychiatry, Vol. 27, No. 3, 2022, p. 1599-1610.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Zhao, X, Ozols, AB, Meyers, KT, Campbell, J, McBride, A, Marballi, KK, Maple, AM, Raskin, C, Mishra, A, Noss, SM, Beck, KL, Khoshaba, R, Bhaskara, A, Godbole, MN, Lish, JR, Kang, P, Hu, C, Palner, M, Overgaard, A, Knudsen, GM & Gallitano, AL 2022, 'Acute sleep deprivation upregulates serotonin 2A receptors in the frontal cortex of mice via the immediate early gene Egr3', Molecular Psychiatry, vol. 27, no. 3, pp. 1599-1610. https://doi.org/10.1038/s41380-021-01390-w

APA

Zhao, X., Ozols, A. B., Meyers, K. T., Campbell, J., McBride, A., Marballi, K. K., Maple, A. M., Raskin, C., Mishra, A., Noss, S. M., Beck, K. L., Khoshaba, R., Bhaskara, A., Godbole, M. N., Lish, J. R., Kang, P., Hu, C., Palner, M., Overgaard, A., ... Gallitano, A. L. (2022). Acute sleep deprivation upregulates serotonin 2A receptors in the frontal cortex of mice via the immediate early gene Egr3. Molecular Psychiatry, 27(3), 1599-1610. https://doi.org/10.1038/s41380-021-01390-w

Vancouver

Zhao X, Ozols AB, Meyers KT, Campbell J, McBride A, Marballi KK et al. Acute sleep deprivation upregulates serotonin 2A receptors in the frontal cortex of mice via the immediate early gene Egr3. Molecular Psychiatry. 2022;27(3):1599-1610. https://doi.org/10.1038/s41380-021-01390-w

Author

Zhao, Xiuli ; Ozols, Annika B. ; Meyers, Kimberly T. ; Campbell, Janet ; McBride, Andrew ; Marballi, Ketan K. ; Maple, Amanda M. ; Raskin, Carren ; Mishra, Abhinav ; Noss, Serena M. ; Beck, Kelsey L. ; Khoshaba, Rami ; Bhaskara, Amulya ; Godbole, Meghna N. ; Lish, James R. ; Kang, Paul ; Hu, Chengcheng ; Palner, Mikael ; Overgaard, Agnete ; Knudsen, Gitte M. ; Gallitano, Amelia L. / Acute sleep deprivation upregulates serotonin 2A receptors in the frontal cortex of mice via the immediate early gene Egr3. In: Molecular Psychiatry. 2022 ; Vol. 27, No. 3. pp. 1599-1610.

Bibtex

@article{05c7ac4c6ff24324880c79f389297bb1,
title = "Acute sleep deprivation upregulates serotonin 2A receptors in the frontal cortex of mice via the immediate early gene Egr3",
abstract = "Serotonin 2A receptors (5-HT(2A)Rs) mediate the hallucinogenic effects of psychedelic drugs and are a key target of the leading class of medications used to treat psychotic disorders. These findings suggest that dysfunction of 5-HT(2A)Rs may contribute to the symptoms of schizophrenia, a mental illness characterized by perceptual and cognitive disturbances. Indeed, numerous studies have found that 5-HT(2A)Rs are reduced in the brains of individuals with schizophrenia. However, the mechanisms that regulate 5-HT2AR expression remain poorly understood. Here, we show that a physiologic environmental stimulus, sleep deprivation, significantly upregulates 5-HT2AR levels in the mouse frontal cortex in as little as 6-8 h (for mRNA and protein, respectively). This induction requires the activity-dependent immediate early gene transcription factor early growth response 3 (Egr3) as it does not occur in Egr3 deficient (-/-) mice. Using chromatin immunoprecipitation, we show that EGR3 protein binds to the promoter of Htr2a, the gene that encodes the 5-HT2AR, in the frontal cortex in vivo, and drives expression of in vitro reporter constructs via two EGR3 binding sites in the Htr2a promoter. These results suggest that EGR3 directly regulates Htr2a expression, and 5-HT2AR levels, in the frontal cortex in response to physiologic stimuli. Analysis of publicly available post-mortem gene expression data revealed that both EGR3 and HTR2A mRNA are reduced in the prefrontal cortex of schizophrenia patients compared to controls. Together these findings suggest a mechanism by which environmental stimuli alter levels of a brain receptor that may mediate the symptoms, and treatment, of mental illness.",
keywords = "MESSENGER-RNA, TRANSCRIPTION FACTOR, ANTIPSYCHOTIC-DRUG, 5-HT2A RECEPTORS, EXPRESSION, SCHIZOPHRENIA, BINDING, CONNECTIVITY, POSTMORTEM, DEPRESSION",
author = "Xiuli Zhao and Ozols, {Annika B.} and Meyers, {Kimberly T.} and Janet Campbell and Andrew McBride and Marballi, {Ketan K.} and Maple, {Amanda M.} and Carren Raskin and Abhinav Mishra and Noss, {Serena M.} and Beck, {Kelsey L.} and Rami Khoshaba and Amulya Bhaskara and Godbole, {Meghna N.} and Lish, {James R.} and Paul Kang and Chengcheng Hu and Mikael Palner and Agnete Overgaard and Knudsen, {Gitte M.} and Gallitano, {Amelia L.}",
year = "2022",
doi = "10.1038/s41380-021-01390-w",
language = "English",
volume = "27",
pages = "1599--1610",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "nature publishing group",
number = "3",

}

RIS

TY - JOUR

T1 - Acute sleep deprivation upregulates serotonin 2A receptors in the frontal cortex of mice via the immediate early gene Egr3

AU - Zhao, Xiuli

AU - Ozols, Annika B.

AU - Meyers, Kimberly T.

AU - Campbell, Janet

AU - McBride, Andrew

AU - Marballi, Ketan K.

AU - Maple, Amanda M.

AU - Raskin, Carren

AU - Mishra, Abhinav

AU - Noss, Serena M.

AU - Beck, Kelsey L.

AU - Khoshaba, Rami

AU - Bhaskara, Amulya

AU - Godbole, Meghna N.

AU - Lish, James R.

AU - Kang, Paul

AU - Hu, Chengcheng

AU - Palner, Mikael

AU - Overgaard, Agnete

AU - Knudsen, Gitte M.

AU - Gallitano, Amelia L.

PY - 2022

Y1 - 2022

N2 - Serotonin 2A receptors (5-HT(2A)Rs) mediate the hallucinogenic effects of psychedelic drugs and are a key target of the leading class of medications used to treat psychotic disorders. These findings suggest that dysfunction of 5-HT(2A)Rs may contribute to the symptoms of schizophrenia, a mental illness characterized by perceptual and cognitive disturbances. Indeed, numerous studies have found that 5-HT(2A)Rs are reduced in the brains of individuals with schizophrenia. However, the mechanisms that regulate 5-HT2AR expression remain poorly understood. Here, we show that a physiologic environmental stimulus, sleep deprivation, significantly upregulates 5-HT2AR levels in the mouse frontal cortex in as little as 6-8 h (for mRNA and protein, respectively). This induction requires the activity-dependent immediate early gene transcription factor early growth response 3 (Egr3) as it does not occur in Egr3 deficient (-/-) mice. Using chromatin immunoprecipitation, we show that EGR3 protein binds to the promoter of Htr2a, the gene that encodes the 5-HT2AR, in the frontal cortex in vivo, and drives expression of in vitro reporter constructs via two EGR3 binding sites in the Htr2a promoter. These results suggest that EGR3 directly regulates Htr2a expression, and 5-HT2AR levels, in the frontal cortex in response to physiologic stimuli. Analysis of publicly available post-mortem gene expression data revealed that both EGR3 and HTR2A mRNA are reduced in the prefrontal cortex of schizophrenia patients compared to controls. Together these findings suggest a mechanism by which environmental stimuli alter levels of a brain receptor that may mediate the symptoms, and treatment, of mental illness.

AB - Serotonin 2A receptors (5-HT(2A)Rs) mediate the hallucinogenic effects of psychedelic drugs and are a key target of the leading class of medications used to treat psychotic disorders. These findings suggest that dysfunction of 5-HT(2A)Rs may contribute to the symptoms of schizophrenia, a mental illness characterized by perceptual and cognitive disturbances. Indeed, numerous studies have found that 5-HT(2A)Rs are reduced in the brains of individuals with schizophrenia. However, the mechanisms that regulate 5-HT2AR expression remain poorly understood. Here, we show that a physiologic environmental stimulus, sleep deprivation, significantly upregulates 5-HT2AR levels in the mouse frontal cortex in as little as 6-8 h (for mRNA and protein, respectively). This induction requires the activity-dependent immediate early gene transcription factor early growth response 3 (Egr3) as it does not occur in Egr3 deficient (-/-) mice. Using chromatin immunoprecipitation, we show that EGR3 protein binds to the promoter of Htr2a, the gene that encodes the 5-HT2AR, in the frontal cortex in vivo, and drives expression of in vitro reporter constructs via two EGR3 binding sites in the Htr2a promoter. These results suggest that EGR3 directly regulates Htr2a expression, and 5-HT2AR levels, in the frontal cortex in response to physiologic stimuli. Analysis of publicly available post-mortem gene expression data revealed that both EGR3 and HTR2A mRNA are reduced in the prefrontal cortex of schizophrenia patients compared to controls. Together these findings suggest a mechanism by which environmental stimuli alter levels of a brain receptor that may mediate the symptoms, and treatment, of mental illness.

KW - MESSENGER-RNA

KW - TRANSCRIPTION FACTOR

KW - ANTIPSYCHOTIC-DRUG

KW - 5-HT2A RECEPTORS

KW - EXPRESSION

KW - SCHIZOPHRENIA

KW - BINDING

KW - CONNECTIVITY

KW - POSTMORTEM

KW - DEPRESSION

U2 - 10.1038/s41380-021-01390-w

DO - 10.1038/s41380-021-01390-w

M3 - Journal article

C2 - 35001075

VL - 27

SP - 1599

EP - 1610

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 3

ER -

ID: 314704685