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Salvianolic acid B alleviates comorbid pain in depression induced by chronic restraint stress through inhibiting GABAergic neuron excitation via an ERK-CREB-BDNF axis-dependent mechanism.
- Source :
-
Journal of Psychiatric Research . Jul2022, Vol. 151, p205-216. 12p. - Publication Year :
- 2022
-
Abstract
- Pain comorbid with depression occurred frequently in clinical settings. This study aims to explore the molecular mechanism underlying antidepressant and analgetic effect of salvianolic acid B (SalB) in comorbid pain in depression induced by chronic restraint stress (CRS), which associates with GABAergic neuron activation in the amygdala and the ERK-CREB-BDNF signaling pathway. The differentially expressed genes related to comorbid pain in CRS-induced depression were screened through bioinformatics analysis. After CRS treatment for 3 weeks, depression-like behaviors were developed in GAD2-tdT mice. The retrograde tracer cholera toxin B subunit combined with retrograde tracer CTB-488 was injected into the parafascicular nucleus of thalamus to project GABAergic neurons to observe the labeling of neurons in the whole brain. After treatment with SalB and ERK-CREB-BDNF signaling pathway inhibitor, CRS mice showed a variety of depression-like behaviors, accompanied by enhanced activity of GABAergic neurons in the amygdala projecting to parafascicular nucleus of thalamus. BDNF underexpression occurred in the CRS mice. Overexpressed BDNF activated ERK-CREB-BDNF signaling pathway to alleviate comorbid pain in CRS-induced depression. After intraperitoneal injection of SalB, the depression-like behaviors and pain threshold in CRS mice were alleviated, the effects of which could be eliminated by ERK-CREB-BDNF signaling pathway antagonist. Collectively, SalB inhibits the excitation of GABAergic neurons in the amygdala and activates the ERK-CREB-BDNF signaling pathway through the parafascicular nucleus of thalamus, whereby alleviating comorbid pain in CRS-induced depression in mice. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00223956
- Volume :
- 151
- Database :
- Academic Search Index
- Journal :
- Journal of Psychiatric Research
- Publication Type :
- Academic Journal
- Accession number :
- 157389218
- Full Text :
- https://doi.org/10.1016/j.jpsychires.2022.04.014