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Rapid-acting and long-lasting antidepressant-like action of (R)-ketamine in Nrf2 knock-out mice: a role of TrkB signaling.

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Title: Rapid-acting and long-lasting antidepressant-like action of (R)-ketamine in Nrf2 knock-out mice: a role of TrkB signaling.
Authors: Qu, Youge (AUTHOR), Shan, Jiajing (AUTHOR), Wang, Siming (AUTHOR), Chang, Lijia (AUTHOR), Pu, Yaoyu (AUTHOR), Wang, Xingming (AUTHOR), Tan, Yunfei (AUTHOR), Yamamoto, Masayuki (AUTHOR), Hashimoto, Kenji (AUTHOR)
Source: European Archives of Psychiatry & Clinical Neuroscience. Apr2021, Vol. 271 Issue 3, p439-446. 8p. 4 Graphs.
Subjects: Ketamine abuse, Mice, Prefrontal cortex, Protein expression, Brain-derived neurotrophic factor
Abstract: The transcription nuclear factor-erythroid factor 2-related factor 2 (Nrf2) plays a key role in inflammation that is involved in depression. We previously reported that Nrf2 knock-out (KO) mice exhibit depression-like phenotypes through systemic inflammation. (R)-ketamine, an enantiomer of ketamine, has rapid-acting and long-lasting antidepressant-like effects in rodents. We investigated whether (R)-ketamine can produce antidepressant-like effects in Nrf2 KO mice. Effects of (R)-ketamine on the depression-like phenotypes in Nrf2 KO mice were examined. Furthermore, the role of TrkB in the antidepressant-like actions of (R)-ketamine was also examined. In the tail-suspension test (TST) and forced swimming test (FST), (R)-ketamine (10 mg/kg) significantly attenuated the increased immobility times of TST and FST in the Nrf2 KO mice. In the sucrose preference test (SPT), (R)-ketamine significantly ameliorated the reduced preference of SPT in Nrf2 KO mice. Decreased expression of synaptic proteins (i.e., GluA1 and PSD-95) in the medial prefrontal cortex (mPFC) of Nrf2 KO mice was significantly ameliorated after a single injection of (R)-ketamine. Furthermore, the pre-treatment with the TrkB antagonist ANA-12 (0.5 mg/kg) significantly blocked the rapid and long-lasting antidepressant-like effects of (R)-ketamine in Nrf2 KO mice. Furthermore, ANA-12 significantly antagonized the beneficial effects of (R)-ketamine on decreased expression of synaptic proteins in the mPFC of Nrf2 KO mice. These findings suggest that (R)-ketamine can produce rapid and long-lasting antidepressant-like actions in Nrf2 KO mice via TrkB signaling. [ABSTRACT FROM AUTHOR]
Copyright of European Archives of Psychiatry & Clinical Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Rapid-acting and long-lasting antidepressant-like action of (R)-ketamine in Nrf2 knock-out mice: a role of TrkB signaling.
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  Data: <searchLink fieldCode="AR" term="%22Qu%2C+Youge%22">Qu, Youge</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Shan%2C+Jiajing%22">Shan, Jiajing</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Siming%22">Wang, Siming</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chang%2C+Lijia%22">Chang, Lijia</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pu%2C+Yaoyu%22">Pu, Yaoyu</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Xingming%22">Wang, Xingming</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Tan%2C+Yunfei%22">Tan, Yunfei</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yamamoto%2C+Masayuki%22">Yamamoto, Masayuki</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hashimoto%2C+Kenji%22">Hashimoto, Kenji</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Archives+of+Psychiatry+%26+Clinical+Neuroscience%22">European Archives of Psychiatry & Clinical Neuroscience</searchLink>. Apr2021, Vol. 271 Issue 3, p439-446. 8p. 4 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Ketamine+abuse%22">Ketamine abuse</searchLink><br /><searchLink fieldCode="DE" term="%22Mice%22">Mice</searchLink><br /><searchLink fieldCode="DE" term="%22Prefrontal+cortex%22">Prefrontal cortex</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+expression%22">Protein expression</searchLink><br /><searchLink fieldCode="DE" term="%22Brain-derived+neurotrophic+factor%22">Brain-derived neurotrophic factor</searchLink>
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  Data: The transcription nuclear factor-erythroid factor 2-related factor 2 (Nrf2) plays a key role in inflammation that is involved in depression. We previously reported that Nrf2 knock-out (KO) mice exhibit depression-like phenotypes through systemic inflammation. (R)-ketamine, an enantiomer of ketamine, has rapid-acting and long-lasting antidepressant-like effects in rodents. We investigated whether (R)-ketamine can produce antidepressant-like effects in Nrf2 KO mice. Effects of (R)-ketamine on the depression-like phenotypes in Nrf2 KO mice were examined. Furthermore, the role of TrkB in the antidepressant-like actions of (R)-ketamine was also examined. In the tail-suspension test (TST) and forced swimming test (FST), (R)-ketamine (10 mg/kg) significantly attenuated the increased immobility times of TST and FST in the Nrf2 KO mice. In the sucrose preference test (SPT), (R)-ketamine significantly ameliorated the reduced preference of SPT in Nrf2 KO mice. Decreased expression of synaptic proteins (i.e., GluA1 and PSD-95) in the medial prefrontal cortex (mPFC) of Nrf2 KO mice was significantly ameliorated after a single injection of (R)-ketamine. Furthermore, the pre-treatment with the TrkB antagonist ANA-12 (0.5 mg/kg) significantly blocked the rapid and long-lasting antidepressant-like effects of (R)-ketamine in Nrf2 KO mice. Furthermore, ANA-12 significantly antagonized the beneficial effects of (R)-ketamine on decreased expression of synaptic proteins in the mPFC of Nrf2 KO mice. These findings suggest that (R)-ketamine can produce rapid and long-lasting antidepressant-like actions in Nrf2 KO mice via TrkB signaling. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of European Archives of Psychiatry & Clinical Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – SubjectFull: Prefrontal cortex
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      – SubjectFull: Brain-derived neurotrophic factor
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              Text: Apr2021
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