Dysfunction of AMPA receptor GluA3 is associated with aggressive behavior in human

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

Standard

Dysfunction of AMPA receptor GluA3 is associated with aggressive behavior in human. / Peng, Shi Xiao; Pei, Jingwen; Rinaldi, Berardo; Chen, Jiang; Ge, Yu Han; Jia, Min; Wang, Jun; Delahaye-Duriez, Andrée; Sun, Jia Hui; Zang, Yan Yu; Shi, Yong Yun; Zhang, Ning; Gao, Xiang; Milani, Donatella; Xu, Xijia; Sheng, Nengyin; Gerard, Benedicte; Zhang, Chen; Bayat, Allan; Liu, Na; Yang, Jian Jun; Shi, Yun Stone.

In: Molecular Psychiatry, Vol. 27, No. 10, 10.2022, p. 4092-4102.

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

Harvard

Peng, SX, Pei, J, Rinaldi, B, Chen, J, Ge, YH, Jia, M, Wang, J, Delahaye-Duriez, A, Sun, JH, Zang, YY, Shi, YY, Zhang, N, Gao, X, Milani, D, Xu, X, Sheng, N, Gerard, B, Zhang, C, Bayat, A, Liu, N, Yang, JJ & Shi, YS 2022, 'Dysfunction of AMPA receptor GluA3 is associated with aggressive behavior in human', Molecular Psychiatry, vol. 27, no. 10, pp. 4092-4102. https://doi.org/10.1038/s41380-022-01659-8

APA

Peng, S. X., Pei, J., Rinaldi, B., Chen, J., Ge, Y. H., Jia, M., Wang, J., Delahaye-Duriez, A., Sun, J. H., Zang, Y. Y., Shi, Y. Y., Zhang, N., Gao, X., Milani, D., Xu, X., Sheng, N., Gerard, B., Zhang, C., Bayat, A., ... Shi, Y. S. (2022). Dysfunction of AMPA receptor GluA3 is associated with aggressive behavior in human. Molecular Psychiatry, 27(10), 4092-4102. https://doi.org/10.1038/s41380-022-01659-8

Vancouver

Peng SX, Pei J, Rinaldi B, Chen J, Ge YH, Jia M et al. Dysfunction of AMPA receptor GluA3 is associated with aggressive behavior in human. Molecular Psychiatry. 2022 Oct;27(10):4092-4102. https://doi.org/10.1038/s41380-022-01659-8

Author

Peng, Shi Xiao ; Pei, Jingwen ; Rinaldi, Berardo ; Chen, Jiang ; Ge, Yu Han ; Jia, Min ; Wang, Jun ; Delahaye-Duriez, Andrée ; Sun, Jia Hui ; Zang, Yan Yu ; Shi, Yong Yun ; Zhang, Ning ; Gao, Xiang ; Milani, Donatella ; Xu, Xijia ; Sheng, Nengyin ; Gerard, Benedicte ; Zhang, Chen ; Bayat, Allan ; Liu, Na ; Yang, Jian Jun ; Shi, Yun Stone. / Dysfunction of AMPA receptor GluA3 is associated with aggressive behavior in human. In: Molecular Psychiatry. 2022 ; Vol. 27, No. 10. pp. 4092-4102.

Bibtex

@article{5c0efcc5a4224f6f933ff21a85516e2f,

title = "Dysfunction of AMPA receptor GluA3 is associated with aggressive behavior in human",

abstract = "Inappropriate aggression in humans hurts the society, families and individuals. The genetic basis for aggressive behavior, however, remains largely elusive. In this study, we identified two rare missense variants in X-linked GRIA3 from male patients who showed syndromes featuring aggressive outbursts. Both G630R and E787G mutations in AMPA receptor GluA3 completely lost their ion channel functions. Furthermore, a guanine-repeat single nucleotide polymorphism (SNP, rs3216834) located in the first intron of human GRIA3 gene was found to regulate GluA3 expression with longer guanine repeats (rs3216834-10G/-11G) suppressing transcription compared to the shorter ones (-7G/-8G/-9G). Importantly, the distribution of rs3216834-10G/-11G was elevated in a male violent criminal sample from Chinese Han population. Using GluA3 knockout mice, we showed that the excitatory neurotransmission and neuronal activity in the medial prefrontal cortex (mPFC) was impaired. Expressing GluA3 back into the mPFC alleviated the aggressive behavior of GluA3 knockout mice, suggesting that the defects in mPFC explained, at least partially, the neural mechanisms underlying the aggressive behavior. Therefore, our study provides compelling evidence that dysfunction of AMPA receptor GluA3 promotes aggressive behavior.",

author = "Peng, {Shi Xiao} and Jingwen Pei and Berardo Rinaldi and Jiang Chen and Ge, {Yu Han} and Min Jia and Jun Wang and Andr{\'e}e Delahaye-Duriez and Sun, {Jia Hui} and Zang, {Yan Yu} and Shi, {Yong Yun} and Ning Zhang and Xiang Gao and Donatella Milani and Xijia Xu and Nengyin Sheng and Benedicte Gerard and Chen Zhang and Allan Bayat and Na Liu and Yang, {Jian Jun} and Shi, {Yun Stone}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2022",

month = oct,

doi = "10.1038/s41380-022-01659-8",

language = "English",

volume = "27",

pages = "4092--4102",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "nature publishing group",

number = "10",

}

RIS

TY - JOUR

T1 - Dysfunction of AMPA receptor GluA3 is associated with aggressive behavior in human

AU - Peng, Shi Xiao

AU - Pei, Jingwen

AU - Rinaldi, Berardo

AU - Chen, Jiang

AU - Ge, Yu Han

AU - Jia, Min

AU - Wang, Jun

AU - Delahaye-Duriez, Andrée

AU - Sun, Jia Hui

AU - Zang, Yan Yu

AU - Shi, Yong Yun

AU - Zhang, Ning

AU - Gao, Xiang

AU - Milani, Donatella

AU - Xu, Xijia

AU - Sheng, Nengyin

AU - Gerard, Benedicte

AU - Zhang, Chen

AU - Bayat, Allan

AU - Liu, Na

AU - Yang, Jian Jun

AU - Shi, Yun Stone

PY - 2022/10

Y1 - 2022/10

N2 - Inappropriate aggression in humans hurts the society, families and individuals. The genetic basis for aggressive behavior, however, remains largely elusive. In this study, we identified two rare missense variants in X-linked GRIA3 from male patients who showed syndromes featuring aggressive outbursts. Both G630R and E787G mutations in AMPA receptor GluA3 completely lost their ion channel functions. Furthermore, a guanine-repeat single nucleotide polymorphism (SNP, rs3216834) located in the first intron of human GRIA3 gene was found to regulate GluA3 expression with longer guanine repeats (rs3216834-10G/-11G) suppressing transcription compared to the shorter ones (-7G/-8G/-9G). Importantly, the distribution of rs3216834-10G/-11G was elevated in a male violent criminal sample from Chinese Han population. Using GluA3 knockout mice, we showed that the excitatory neurotransmission and neuronal activity in the medial prefrontal cortex (mPFC) was impaired. Expressing GluA3 back into the mPFC alleviated the aggressive behavior of GluA3 knockout mice, suggesting that the defects in mPFC explained, at least partially, the neural mechanisms underlying the aggressive behavior. Therefore, our study provides compelling evidence that dysfunction of AMPA receptor GluA3 promotes aggressive behavior.

AB - Inappropriate aggression in humans hurts the society, families and individuals. The genetic basis for aggressive behavior, however, remains largely elusive. In this study, we identified two rare missense variants in X-linked GRIA3 from male patients who showed syndromes featuring aggressive outbursts. Both G630R and E787G mutations in AMPA receptor GluA3 completely lost their ion channel functions. Furthermore, a guanine-repeat single nucleotide polymorphism (SNP, rs3216834) located in the first intron of human GRIA3 gene was found to regulate GluA3 expression with longer guanine repeats (rs3216834-10G/-11G) suppressing transcription compared to the shorter ones (-7G/-8G/-9G). Importantly, the distribution of rs3216834-10G/-11G was elevated in a male violent criminal sample from Chinese Han population. Using GluA3 knockout mice, we showed that the excitatory neurotransmission and neuronal activity in the medial prefrontal cortex (mPFC) was impaired. Expressing GluA3 back into the mPFC alleviated the aggressive behavior of GluA3 knockout mice, suggesting that the defects in mPFC explained, at least partially, the neural mechanisms underlying the aggressive behavior. Therefore, our study provides compelling evidence that dysfunction of AMPA receptor GluA3 promotes aggressive behavior.

U2 - 10.1038/s41380-022-01659-8

DO - 10.1038/s41380-022-01659-8

M3 - Journal article

C2 - 35697757

AN - SCOPUS:85131876195

VL - 27

SP - 4092

EP - 4102

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 10

ER -

ID: 389675852

Department of Economics