GluN2B on adult-born granule cells modulates (R,S)-ketamine's rapid-acting effects in mice.

Autor:	Bulthuis NE; Doctoral Program in Neurobiology and Behavior (NB&B), Columbia University, New York, NY, USA., McGowan JC; Doctoral Program in Neurobiology and Behavior (NB&B), Columbia University, New York, NY, USA., Ladner LR; Department of Neuroscience, Barnard College, New York, NY, USA., LaGamma CT; Division of Systems Neuroscience, Research Foundation for Mental Hygiene, Inc. (RFMH)/New York State Psychiatric Institute (NYSPI), New York, NY, USA.; Department of Psychiatry, Columbia University Irving Medical Center (CUIMC), New York, NY, USA., Lim SC; Doctoral Program in Neurobiology and Behavior (NB&B), Columbia University, New York, NY, USA.; Division of Systems Neuroscience, Research Foundation for Mental Hygiene, Inc. (RFMH)/New York State Psychiatric Institute (NYSPI), New York, NY, USA.; Department of Psychiatry, Columbia University Irving Medical Center (CUIMC), New York, NY, USA.; Medical Science Training Program (MSTP), Columbia University Irving Medical Center (CUIMC), New York, NY, USA., Shubeck CX; Columbia University in the City of New York, New York, NY, USA., Brachman RA; Department of Psychiatry, Columbia University Irving Medical Center (CUIMC), New York, NY, USA., Sydnor E; Division of Systems Neuroscience, Research Foundation for Mental Hygiene, Inc. (RFMH)/New York State Psychiatric Institute (NYSPI), New York, NY, USA., Pavlova IP; Division of Systems Neuroscience, Research Foundation for Mental Hygiene, Inc. (RFMH)/New York State Psychiatric Institute (NYSPI), New York, NY, USA., Seo DO; Department of Neuroscience, University of Texas at Austin, Austin, TX, USA., Drew MR; Department of Neuroscience, University of Texas at Austin, Austin, TX, USA., Denny CA; Division of Systems Neuroscience, Research Foundation for Mental Hygiene, Inc. (RFMH)/New York State Psychiatric Institute (NYSPI), New York, NY, USA.; Department of Psychiatry, Columbia University Irving Medical Center (CUIMC), New York, NY, USA.
Jazyk:	angličtina
Zdroj:	The international journal of neuropsychopharmacology [Int J Neuropsychopharmacol] 2024 Sep 06. Date of Electronic Publication: 2024 Sep 06.
DOI:	10.1093/ijnp/pyae036
Abstrakt:	Background: Standard antidepressant treatments often take weeks to reach efficacy and are ineffective for many patients. (R,S)-ketamine, an N-methyl-D-aspartate (NMDA) antagonist, has been shown to be a rapid-acting antidepressant and to decrease depressive symptoms within hours of administration. While previous studies have shown the importance of the GluN2B subunit of the NMDA receptor (NMDAR) on interneurons in the medial prefrontal cortex (mPFC), no study has investigated the influence of GluN2B-expressing adult-born granule cells (abGCs). Methods: Here, we examined whether (R,S)-ketamine's efficacy depends upon these adult-born hippocampal neurons using a genetic strategy to selectively ablate the GluN2B subunit of the NMDAR from Nestin+ cells in male and female mice, tested across an array of standard behavioral assays. Results: We report that in male mice, GluN2B expression on 6-week-old adult-born neurons is necessary for (R,S)-ketamine's effects on behavioral despair in the forced swim test (FST) and on hyponeophagia in the novelty suppressed feeding (NSF) paradigm, as well on fear behavior following contextual fear conditioning (CFC). In female mice, GluN2B expression is necessary for effects on hyponeophagia in the NSF. These effects were not replicated when ablating GluN2B from 2-week-old adult-born neurons. We also find that ablating neurogenesis increases fear expression in CFC, which is buffered by (R,S)-ketamine administration. Conclusions: In line with previous studies, these results suggest that 6-week-old adult-born hippocampal neurons expressing GluN2B partially modulate (R,S)-ketamine's rapid-acting effects. Future work targeting these 6-week-old adult-born neurons may prove beneficial for increasing the efficacy of (R,S)-ketamine. (© The Author(s) 2024. Published by Oxford University Press on behalf of CINP.)
Databáze:	MEDLINE
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