NMDAR2B tyrosine phosphorylation regulates anxiety-like behavior and CRF expression in the amygdala

Mina Delawary, Tohru Tezuka, Yuji Kiyama, Kazumasa Yokoyama, Takeshi Inoue, Satoko Takai, Ryota Hashimoto, Hisashi Umemori, Toshiya Manabe, Tadashi Yamamoto, Takanobu Nakazawa

Research output: Contribution to journalArticle

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Abstract

Background: Anxiety disorders are a highly prevalent and disabling class of psychiatric disorders. There is growing evidence implicating the glutamate system in the pathophysiology and treatment of anxiety disorders, though the molecular mechanism by which the glutamate system regulates anxiety-like behavior remains unclear. Results. In this study, we provide evidence suggesting that tyrosine phosphorylation of the NMDA receptor, an ionotropic glutamate receptor, contributes to anxiety-like behavior. The GluN2B subunit of the NMDA receptor is tyrosine-phosphorylated: Tyr-1472 is the major phosphorylation site. Homozygous knock-in mice that express a Tyr-1472-Phe mutant of GluN2B, which prevents phosphorylation of this site, show enhanced anxiety-like behavior in the elevated plus-maze test. Expression of corticotropin-releasing factor (CRF), which is important for the regulation of anxiety-like behavior, is increased in the amygdala of the knock-in mice. Furthermore, injection of CRF receptor antagonist attenuated the enhanced anxiety-like behavior of the knock-in mice. We also show that elevated plus-maze exposure simultaneously induced de-phosphorylation of Tyr-1472 and increased CRF expression. Conclusions. These data suggest that Tyr-1472 phosphorylation on GluN2B is important for anxiety-like behavior by negative regulation of CRF expression in the amygdala.

Original languageEnglish
Article number37
JournalMolecular brain
Volume3
Issue number1
DOIs
Publication statusPublished - 02-12-2010

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Corticotropin-Releasing Hormone
Amygdala
Tyrosine
Anxiety
Phosphorylation
Anxiety Disorders
N-Methyl-D-Aspartate Receptors
Glutamic Acid
Corticotropin-Releasing Hormone Receptors
Ionotropic Glutamate Receptors
Psychiatry
Injections

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Delawary, Mina ; Tezuka, Tohru ; Kiyama, Yuji ; Yokoyama, Kazumasa ; Inoue, Takeshi ; Takai, Satoko ; Hashimoto, Ryota ; Umemori, Hisashi ; Manabe, Toshiya ; Yamamoto, Tadashi ; Nakazawa, Takanobu. / NMDAR2B tyrosine phosphorylation regulates anxiety-like behavior and CRF expression in the amygdala. In: Molecular brain. 2010 ; Vol. 3, No. 1.
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Delawary, M, Tezuka, T, Kiyama, Y, Yokoyama, K, Inoue, T, Takai, S, Hashimoto, R, Umemori, H, Manabe, T, Yamamoto, T & Nakazawa, T 2010, 'NMDAR2B tyrosine phosphorylation regulates anxiety-like behavior and CRF expression in the amygdala', Molecular brain, vol. 3, no. 1, 37. https://doi.org/10.1186/1756-6606-3-37

NMDAR2B tyrosine phosphorylation regulates anxiety-like behavior and CRF expression in the amygdala. / Delawary, Mina; Tezuka, Tohru; Kiyama, Yuji; Yokoyama, Kazumasa; Inoue, Takeshi; Takai, Satoko; Hashimoto, Ryota; Umemori, Hisashi; Manabe, Toshiya; Yamamoto, Tadashi; Nakazawa, Takanobu.

In: Molecular brain, Vol. 3, No. 1, 37, 02.12.2010.

Research output: Contribution to journalArticle

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T1 - NMDAR2B tyrosine phosphorylation regulates anxiety-like behavior and CRF expression in the amygdala

AU - Delawary, Mina

AU - Tezuka, Tohru

AU - Kiyama, Yuji

AU - Yokoyama, Kazumasa

AU - Inoue, Takeshi

AU - Takai, Satoko

AU - Hashimoto, Ryota

AU - Umemori, Hisashi

AU - Manabe, Toshiya

AU - Yamamoto, Tadashi

AU - Nakazawa, Takanobu

PY - 2010/12/2

Y1 - 2010/12/2

N2 - Background: Anxiety disorders are a highly prevalent and disabling class of psychiatric disorders. There is growing evidence implicating the glutamate system in the pathophysiology and treatment of anxiety disorders, though the molecular mechanism by which the glutamate system regulates anxiety-like behavior remains unclear. Results. In this study, we provide evidence suggesting that tyrosine phosphorylation of the NMDA receptor, an ionotropic glutamate receptor, contributes to anxiety-like behavior. The GluN2B subunit of the NMDA receptor is tyrosine-phosphorylated: Tyr-1472 is the major phosphorylation site. Homozygous knock-in mice that express a Tyr-1472-Phe mutant of GluN2B, which prevents phosphorylation of this site, show enhanced anxiety-like behavior in the elevated plus-maze test. Expression of corticotropin-releasing factor (CRF), which is important for the regulation of anxiety-like behavior, is increased in the amygdala of the knock-in mice. Furthermore, injection of CRF receptor antagonist attenuated the enhanced anxiety-like behavior of the knock-in mice. We also show that elevated plus-maze exposure simultaneously induced de-phosphorylation of Tyr-1472 and increased CRF expression. Conclusions. These data suggest that Tyr-1472 phosphorylation on GluN2B is important for anxiety-like behavior by negative regulation of CRF expression in the amygdala.

AB - Background: Anxiety disorders are a highly prevalent and disabling class of psychiatric disorders. There is growing evidence implicating the glutamate system in the pathophysiology and treatment of anxiety disorders, though the molecular mechanism by which the glutamate system regulates anxiety-like behavior remains unclear. Results. In this study, we provide evidence suggesting that tyrosine phosphorylation of the NMDA receptor, an ionotropic glutamate receptor, contributes to anxiety-like behavior. The GluN2B subunit of the NMDA receptor is tyrosine-phosphorylated: Tyr-1472 is the major phosphorylation site. Homozygous knock-in mice that express a Tyr-1472-Phe mutant of GluN2B, which prevents phosphorylation of this site, show enhanced anxiety-like behavior in the elevated plus-maze test. Expression of corticotropin-releasing factor (CRF), which is important for the regulation of anxiety-like behavior, is increased in the amygdala of the knock-in mice. Furthermore, injection of CRF receptor antagonist attenuated the enhanced anxiety-like behavior of the knock-in mice. We also show that elevated plus-maze exposure simultaneously induced de-phosphorylation of Tyr-1472 and increased CRF expression. Conclusions. These data suggest that Tyr-1472 phosphorylation on GluN2B is important for anxiety-like behavior by negative regulation of CRF expression in the amygdala.

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