NLRP1 inflammasome contributes to chronic stress-induced depressive-like behaviors in mice
| Autor: | Ya-Jing Zhu, Li-Zhong Xu, Jun-Juan Fan, Jun Zhou, Bo Gao, Wen-Ning Wu, Ao-Qi Song, Yu-Ling Wang |
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| Rok vydání: | 2020 |
| Předmět: |
Male
MDD 0301 basic medicine medicine.medical_specialty Inflammasomes Immunology lcsh:RC346-429 Proinflammatory cytokine Pathogenesis Social defeat Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Animal models of depression Internal medicine NLRP1 inflammasome medicine Animals CXCL1/CXCR2 Chronic stress lcsh:Neurology. Diseases of the nervous system Adaptor Proteins Signal Transducing Behavior Animal Depression business.industry Research General Neuroscience Inflammasome BDNF 030104 developmental biology Endocrinology Neurology Antidepressant Apoptosis Regulatory Proteins business Stress Psychological 030217 neurology & neurosurgery Signal Transduction medicine.drug Behavioural despair test |
| Zdroj: | Journal of Neuroinflammation Journal of Neuroinflammation, Vol 17, Iss 1, Pp 1-13 (2020) |
| ISSN: | 1742-2094 |
| DOI: | 10.1186/s12974-020-01848-8 |
| Popis: | Background Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, and inflammation has been considered crucial components of the pathogenesis of depression. NLRP1 inflammasome-driven inflammatory response is believed to participate in many neurological disorders. However, it is unclear whether NLRP1 inflammasome is implicated in the development of depression. Methods Animal models of depression were established by four different chronic stress stimuli including chronic unpredictable mild stress (CUMS), chronic restrain stress (CRS), chronic social defeat stress (CSDS), and repeat social defeat stress (RSDS). Depressive-like behaviors were determined by sucrose preference test (SPT), forced swim test (FST), tail-suspension test (TST), open-field test (OFT), social interaction test (SIT), and light-dark test (LDT). The expression of NLRP1 inflammasome complexes, BDNF, and CXCL1/CXCR2 were tested by western blot and quantitative real-time PCR. The levels of inflammatory cytokines were tested by enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. Results Chronic stress stimuli activated hippocampal NLRP1 inflammasome and promoted the release of pro-inflammatory cytokines IL-1β, IL-18, IL-6, and TNF-α in mice. Hippocampal Nlrp1a knockdown prevented NLRP1 inflammasome-driven inflammatory response and ameliorated stress-induced depressive-like behaviors. Also, chronic stress stimuli caused the increase in hippocampal CXCL1/CXCR2 expression and low BDNF levels in mice. Interestingly, Nlrp1a knockdown inhibited the up-regulation of CXCL1/CXCR2 expression and restored BDNF levels in the hippocampus. Conclusions NLRP1 inflammasome-driven inflammatory response contributes to chronic stress induced depressive-like behaviors and the mechanism may be related to CXCL1/CXCR2/BDNF signaling pathway. Thus, NLRP1 inflammasome could become a potential antidepressant target. |
| Databáze: | OpenAIRE |
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