Disrupting the α7nAChR–NR2A protein complex exerts antidepressant-like effects
Abstract Major depressive disorder (MDD) is associated with significant morbidity and mortality. Most antidepressant medications target the serotonin and norepinephrine transporters, but a significant minority of patients do not respond to treatment and novel therapeutic targets are needed. We previ...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-07-01
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| Series: | Molecular Brain |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13041-021-00817-3 |
| _version_ | 1818859590775734272 |
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| author | Anlong Jiang Ping Su Shupeng Li Albert H. C. Wong Fang Liu |
| author_facet | Anlong Jiang Ping Su Shupeng Li Albert H. C. Wong Fang Liu |
| author_sort | Anlong Jiang |
| collection | DOAJ |
| description | Abstract Major depressive disorder (MDD) is associated with significant morbidity and mortality. Most antidepressant medications target the serotonin and norepinephrine transporters, but a significant minority of patients do not respond to treatment and novel therapeutic targets are needed. We previously identified a protein complex composed of the α7 nicotinic acetylcholine receptor (nAChR) and NMDA glutamate receptors (NMDARs), through which α7nAChR upregulates NMDAR function. Disruption of the α7nAChR–NMDAR complex with an interfering peptide blocked α7nAChR-mediated upregulation of NMDAR function and cue-induced reinstatement of nicotine seeking in rat models of relapse. Here we report that disrupting the α7nAChR–NMDAR complex with the interfering peptide also has antidepressant-like effects in the forced swim test (FST), a common rat behaviour screening test for antidepressant effects. Furthermore, the interfering peptide significantly increases extracellular signal-regulated kinase (ERK) activity in the animals subjected to the FST. Our results provide a novel potential therapeutic target for the development of new antidepressant medications. |
| first_indexed | 2024-12-19T09:14:36Z |
| format | Article |
| id | doaj.art-1fe716ab1f0049dd8a20b8d39f2a7f62 |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-19T09:14:36Z |
| publishDate | 2021-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-1fe716ab1f0049dd8a20b8d39f2a7f622022-12-21T20:28:07ZengBMCMolecular Brain1756-66062021-07-0114111110.1186/s13041-021-00817-3Disrupting the α7nAChR–NR2A protein complex exerts antidepressant-like effectsAnlong Jiang0Ping Su1Shupeng Li2Albert H. C. Wong3Fang Liu4Campbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthCampbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthCampbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthCampbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthCampbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthAbstract Major depressive disorder (MDD) is associated with significant morbidity and mortality. Most antidepressant medications target the serotonin and norepinephrine transporters, but a significant minority of patients do not respond to treatment and novel therapeutic targets are needed. We previously identified a protein complex composed of the α7 nicotinic acetylcholine receptor (nAChR) and NMDA glutamate receptors (NMDARs), through which α7nAChR upregulates NMDAR function. Disruption of the α7nAChR–NMDAR complex with an interfering peptide blocked α7nAChR-mediated upregulation of NMDAR function and cue-induced reinstatement of nicotine seeking in rat models of relapse. Here we report that disrupting the α7nAChR–NMDAR complex with the interfering peptide also has antidepressant-like effects in the forced swim test (FST), a common rat behaviour screening test for antidepressant effects. Furthermore, the interfering peptide significantly increases extracellular signal-regulated kinase (ERK) activity in the animals subjected to the FST. Our results provide a novel potential therapeutic target for the development of new antidepressant medications.https://doi.org/10.1186/s13041-021-00817-3α7 Nicotinic acetylcholine receptor (α7nAChR)Extracellular signal-regulated kinase (ERK)Forced swim test (FST)Major depressive disorder (MDD)NMDA glutamate receptors (NMDARs) |
| spellingShingle | Anlong Jiang Ping Su Shupeng Li Albert H. C. Wong Fang Liu Disrupting the α7nAChR–NR2A protein complex exerts antidepressant-like effects Molecular Brain α7 Nicotinic acetylcholine receptor (α7nAChR) Extracellular signal-regulated kinase (ERK) Forced swim test (FST) Major depressive disorder (MDD) NMDA glutamate receptors (NMDARs) |
| title | Disrupting the α7nAChR–NR2A protein complex exerts antidepressant-like effects |
| title_full | Disrupting the α7nAChR–NR2A protein complex exerts antidepressant-like effects |
| title_fullStr | Disrupting the α7nAChR–NR2A protein complex exerts antidepressant-like effects |
| title_full_unstemmed | Disrupting the α7nAChR–NR2A protein complex exerts antidepressant-like effects |
| title_short | Disrupting the α7nAChR–NR2A protein complex exerts antidepressant-like effects |
| title_sort | disrupting the α7nachr nr2a protein complex exerts antidepressant like effects |
| topic | α7 Nicotinic acetylcholine receptor (α7nAChR) Extracellular signal-regulated kinase (ERK) Forced swim test (FST) Major depressive disorder (MDD) NMDA glutamate receptors (NMDARs) |
| url | https://doi.org/10.1186/s13041-021-00817-3 |
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