Dataset Information


Gene deficiency and pharmacological inhibition of caspase-1 confers resilience to chronic social defeat stress via regulating the stability of surface AMPARs.

ABSTRACT: Both inflammatory processes and glutamatergic systems have been implicated in the pathophysiology of mood-related disorders. However, the role of caspase-1, a classic inflammatory caspase, in behavioral responses to chronic stress remains largely unknown. To address this issue, we examined the effects and underlying mechanisms of caspase-1 on preclinical murine models of depression. We found that loss of caspase-1 expression in Caspase-1-/- knockout mice alleviated chronic stress-induced depression-like behaviors, whereas overexpression of caspase-1 in the hippocampus of wild-type (WT) mice was sufficient to induce depression- and anxiety-like behaviors. Furthermore, chronic stress reduced glutamatergic neurotransmission and decreased surface expression of glutamate receptors in hippocampal pyramidal neurons of WT mice, but not Caspase-1-/- mice. Importantly, pharmacological inhibition of caspase-1-interleukin-1? (IL-1?) signaling pathway prevented the depression-like behaviors and the decrease in surface expression of ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in stressed WT mice. Finally, the effects of chronic stress on both depression- and anxiety-like behaviors can be mimicked by exogenous intracerebroventricular (i.c.v.) administration of IL-1? in both WT and Caspase-1-/- mice. Taken together, our findings demonstrate that an increase in the caspase-1/IL-1? axis facilitates AMPAR internalization in the hippocampus, which dysregulates glutamatergic synaptic transmission, eventually resulting in depression-like behaviors. These results may represent an endophenotype for chronic stress-induced depression.


PROVIDER: S-EPMC5822452 | BioStudies | 2018-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC5424302 | BioStudies
2017-01-01 | S-EPMC5269558 | BioStudies
2019-01-01 | S-EPMC6960224 | BioStudies
2019-01-01 | S-EPMC6478702 | BioStudies
2019-01-01 | S-EPMC6727781 | BioStudies
1000-01-01 | S-EPMC5599541 | BioStudies
2016-01-01 | S-EPMC4879188 | BioStudies
2017-01-01 | S-EPMC5726568 | BioStudies
2014-01-01 | S-EPMC4167209 | BioStudies
2020-01-01 | S-EPMC7281929 | BioStudies