Ketamine Induces Lasting Antidepressant Effects by Modulating the NMDAR/CaMKII-Mediated Synaptic Plasticity of the Hippocampal Dentate Gyrus in Depressive Stroke Model
Copyright © 2021 Idriss Ali Abdoulaye et al.
| Veröffentlicht in: | Neural plasticity. - 1998. - 2021(2021) vom: 30., Seite 6635084 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2021
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| Zugriff auf das übergeordnete Werk: | Neural plasticity |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Antidepressive Agents Disks Large Homolog 4 Protein Dlg4 protein, rat Receptors, N-Methyl-D-Aspartate Ketamine 690G0D6V8H Calcium-Calmodulin-Dependent Protein Kinase Type 2 EC 2.7.11.17 |
| Zusammenfassung: | Copyright © 2021 Idriss Ali Abdoulaye et al. Background: Ketamine has been shown to possess lasting antidepressant properties. However, studies of the mechanisms involved in its effects on poststroke depression are nonexistent Methods: To investigate these mechanisms, Sprague-Dawley rats were treated with a single local dose of ketamine after middle cerebral artery occlusion and chronic unpredicted mild stress. The effects on the hippocampal dentate gyrus were analyzed through assessment of the N-methyl-D-aspartate receptor/calcium/calmodulin-dependent protein kinase II (NMDAR/CaMKII) pathway, synaptic plasticity, and behavioral tests Results: Ketamine administration rapidly exerted significant and lasting improvements of depressive symptoms. The biochemical analysis showed rapid, selective upregulation and downregulation of the NMDAR2-β and NMDAR2-α subtypes as well as their downstream signaling proteins β-CaMKII and α-phosphorylation in the dentate gyrus, respectively. Furthermore, the colocalization analysis indicated a significant and selectively increased conjunction of β-CaMKII and postsynaptic density protein 95 (PSD95) coupled with a notable decrease in NMDAR2-β association with PSD95 after ketamine treatment. These changes translated into significant and extended synaptic plasticity in the dentate gyrus Conclusions: These findings not only suggest that ketamine represents a viable candidate for the treatment of poststroke depression but also that ketamine's lasting antidepressant effects might be achieved through modulation of NMDAR/CaMKII-induced synaptic plasticity in key brain regions |
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| Beschreibung: | Date Completed 06.12.2021 Date Revised 16.07.2022 published: Electronic-eCollection Citation Status MEDLINE |
| ISSN: | 1687-5443 |
| DOI: | 10.1155/2021/6635084 |