Aging Promotes Chronic Stress-Induced Depressive-Like Behavior by Activating NLRP1 Inflammasome-Driven Inflammatory Signaling in Mice. 2022

Ya-Jing Zhu, and Jun-Juan Fan, and Fang-Yi Wu, and Ming Zhang, and Ao-Qi Song, and Yong Li, and Yan-Kun Li, and Wen-Ning Wu
Department of Pharmacology, School of Basic Medical Sciences, and Key Laboratory of Anti-Inflammatory and Immunopharmacology, Anhui Medical University, Hefei, 230032, People's Republic of China.

NLRP1 inflammasome has been reported to participate in many neurological disorders. Our previous study has demonstrated that NLRP1 inflammasome is implicated in chronic stress-induced depressive-like behaviors in mice. Age has been reported to be related to depression. Here we examine whether NLRP1 inflammasome is involved in the effect of age on depressive disorder. Two chronic stress stimuli, chronic social defeat stress (CSDS) and repeat social defeat stress (RSDS), were used to establish a depression model in mice of different ages. We found that aged mice exhibited worse depressive-like behaviors and locomotor activity compared to young mice. Interestingly, the expression of hippocampal NLRP1 inflammasome complexes and the levels of the inflammatory cytokines were increased in an age-dependent manner. Also, chronic stress-induced increase in the expression of the hippocampal chemokine C-X-C motif ligand 1 (CXCL1), and its cognate receptor, CXC-motif receptor 2 (CXCR2), was more remarkable in aged mice than that in young mice. Moreover, aged mice exhibited lower hippocampal BDNF levels compared to young mice. Hippocampal Nlrp1a knockdown reduced the levels of pro-inflammatory cytokines and the expression of CXCL1/CXCR2, restored BDNF levels, and alleviated chronic stress-induced depressive-like behaviors in aged mice. Our results suggest that NLRP1 inflammasome-CXCL1/CXCR2-BDNF signaling contributes to the effect of age on chronic stress-induced depressive-like behavior in mice.

UI MeSH Term Description Entries
D003863 Depression Depressive states usually of moderate intensity in contrast with MAJOR DEPRESSIVE DISORDER present in neurotic and psychotic disorders. Depressive Symptoms,Emotional Depression,Depression, Emotional,Depressive Symptom,Symptom, Depressive
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000375 Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time. Senescence,Aging, Biological,Biological Aging
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013315 Stress, Psychological Stress wherein emotional factors predominate. Cumulative Stress, Psychological,Emotional Stress,Individual Stressors,Life Stress,Psychological Cumulative Stress,Psychological Stress Experience,Psychological Stress Overload,Psychologically Stressful Conditions,Stress Experience, Psychological,Stress Measurement, Psychological,Stress Overload, Psychological,Stress Processes, Psychological,Stress, Emotional,Stressful Conditions, Psychological,Psychological Stress,Stress, Psychologic,Stressor, Psychological,Condition, Psychological Stressful,Condition, Psychologically Stressful,Conditions, Psychologically Stressful,Cumulative Stresses, Psychological,Experience, Psychological Stress,Individual Stressor,Life Stresses,Measurement, Psychological Stress,Overload, Psychological Stress,Psychologic Stress,Psychological Cumulative Stresses,Psychological Stress Experiences,Psychological Stress Measurement,Psychological Stress Measurements,Psychological Stress Overloads,Psychological Stress Processe,Psychological Stress Processes,Psychological Stresses,Psychological Stressful Condition,Psychological Stressful Conditions,Psychological Stressor,Psychological Stressors,Psychologically Stressful Condition,Stress Experiences, Psychological,Stress Processe, Psychological,Stress, Life,Stress, Psychological Cumulative,Stressful Condition, Psychological,Stressful Condition, Psychologically,Stressor, Individual
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D058847 Inflammasomes Multiprotein complexes that mediate the activation of CASPASE-1. Dysregulation of inflammasomes has also been linked to a number of autoinflammatory and autoimmune disorders. Inflammasome,Pyroptosome,Pyroptosomes
D019208 Brain-Derived Neurotrophic Factor A member of the nerve growth factor family of trophic factors. In the brain BDNF has a trophic action on retinal, cholinergic, and dopaminergic neurons, and in the peripheral nervous system it acts on both motor and sensory neurons. (From Kendrew, The Encyclopedia of Molecular Biology, 1994) BDNF,Brain Derived Neurotrophic Factor,Factor, Brain-Derived Neurotrophic,Neurotrophic Factor, Brain-Derived

Related Publications

Ya-Jing Zhu, and Jun-Juan Fan, and Fang-Yi Wu, and Ming Zhang, and Ao-Qi Song, and Yong Li, and Yan-Kun Li, and Wen-Ning Wu
January 2024, Journal of neuroinflammation,
Ya-Jing Zhu, and Jun-Juan Fan, and Fang-Yi Wu, and Ming Zhang, and Ao-Qi Song, and Yong Li, and Yan-Kun Li, and Wen-Ning Wu
January 2019, Frontiers in molecular neuroscience,
Ya-Jing Zhu, and Jun-Juan Fan, and Fang-Yi Wu, and Ming Zhang, and Ao-Qi Song, and Yong Li, and Yan-Kun Li, and Wen-Ning Wu
December 2023, European journal of pharmacology,
Ya-Jing Zhu, and Jun-Juan Fan, and Fang-Yi Wu, and Ming Zhang, and Ao-Qi Song, and Yong Li, and Yan-Kun Li, and Wen-Ning Wu
October 2023, EMBO molecular medicine,
Ya-Jing Zhu, and Jun-Juan Fan, and Fang-Yi Wu, and Ming Zhang, and Ao-Qi Song, and Yong Li, and Yan-Kun Li, and Wen-Ning Wu
July 2012, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Ya-Jing Zhu, and Jun-Juan Fan, and Fang-Yi Wu, and Ming Zhang, and Ao-Qi Song, and Yong Li, and Yan-Kun Li, and Wen-Ning Wu
July 2022, Science (New York, N.Y.),
Ya-Jing Zhu, and Jun-Juan Fan, and Fang-Yi Wu, and Ming Zhang, and Ao-Qi Song, and Yong Li, and Yan-Kun Li, and Wen-Ning Wu
October 2023, The Journal of experimental medicine,
Ya-Jing Zhu, and Jun-Juan Fan, and Fang-Yi Wu, and Ming Zhang, and Ao-Qi Song, and Yong Li, and Yan-Kun Li, and Wen-Ning Wu
August 2018, Brain, behavior, and immunity,
Ya-Jing Zhu, and Jun-Juan Fan, and Fang-Yi Wu, and Ming Zhang, and Ao-Qi Song, and Yong Li, and Yan-Kun Li, and Wen-Ning Wu
May 2019, Journal of psychopharmacology (Oxford, England),
Ya-Jing Zhu, and Jun-Juan Fan, and Fang-Yi Wu, and Ming Zhang, and Ao-Qi Song, and Yong Li, and Yan-Kun Li, and Wen-Ning Wu
January 2016, Pharmacology, biochemistry, and behavior,
Copied contents to your clipboard!