Activation of the p11/SMARCA3/Neurensin-2 pathway in parvalbumin interneurons mediates the response to chronic antidepressants
| Autor: | Yotam Sagi, Paul Greengard, Kathryn A. McCabe, Lucian Medrihan, Gali Umschweif |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cell type Hippocampus Chromatin Remodeling Factor Hippocampal formation Article 03 medical and health sciences Cellular and Molecular Neuroscience Glutamatergic 0302 clinical medicine Downregulation and upregulation Interneurons Animals Molecular Biology biology Depression Membrane Proteins Antidepressive Agents DNA-Binding Proteins Mice Inbred C57BL Psychiatry and Mental health Parvalbumins 030104 developmental biology nervous system biology.protein Antidepressant Neuroscience Selective Serotonin Reuptake Inhibitors 030217 neurology & neurosurgery Parvalbumin Transcription Factors |
| Zdroj: | Molecular Psychiatry |
| ISSN: | 1476-5578 1359-4184 |
| DOI: | 10.1038/s41380-021-01059-4 |
| Popis: | The delayed behavioral response to chronic antidepressants depends on dynamic changes in the hippocampus. It was suggested that the antidepressant protein p11 and the chromatin remodeling factor SMARCA3 mediate this delayed response by inducing transcriptional changes in hippocampal neurons. However, what target genes are regulated by the p11/SMARCA3 complex to mediate the behavioral response to antidepressants, and what cell type mediates these molecular changes remain unknown. Here we report that the p11/SMARCA3 complex represses Neurensin-2 transcription in hippocampal parvalbumin-expressing interneurons after chronic treatment with Selective Serotonin Reuptake Inhibitors (SSRI). The behavioral response to antidepressants requires upregulation of p11, accumulation of SMARCA3 in the cell nucleus, and a consequent repression of Neurensin-2 transcription in these interneurons. We elucidate a functional role for p11/SMARCA3/Neurensin-2 pathway in regulating AMPA-receptor signaling in parvalbumin-expressing interneurons, a function that is enhanced by chronic treatment with SSRIs. These results link SSRIs to dynamic glutamatergic changes and implicate p11/SMARCA3/Neurensin-2 pathway in the development of more specific and efficient therapeutic strategies for neuropsychiatric disorders. |
| Databáze: | OpenAIRE |
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