Hippocampal PKR/NLRP1 Inflammasome Pathway Is Required for the Depression-Like Behaviors in Rats with Neuropathic Pain. (1st August 2019)

• Record Type: Journal Article
• Authors: Li, Qian; Liu, Shenbin; Zhu, Xiaocang; Mi, Wenli; Maoying, Qiliang; Wang, Jun; Yu, Jin; Wang, Yanqing
• Is Part Of: Neuroscience. Volume 412(2019)
• Page Start: 16
• Page End: 28
• Publication Date: 2019-08-01
• Subjects: 2-AP 2-Aminopurine -- ASC Apoptosis-associated speck-like protein containing a caspase-activating recruitment domain -- CARD Caspase-activating recruitment domain -- CCI Chronic constriction injury -- CNS Central nervous system -- DAMPs Damage-associated molecular patterns -- ELISA Enzyme-linked immunosorbent assay -- EPM Elevated plus maze -- FST Forced swimming test -- GFAP Glial fibrillary acidic protein -- IL Interleukin -- NeuN Neuron-specific Nuclear Protein -- NLRP The Nod-like receptor protein -- OFT Open field test -- PAMPs Pathogen-associated molecular patterns -- PBS Phosphate-buffered solution -- PKR Double-stranded RNA-dependent protein kinase -- PWL Paw withdrawal latency -- SEM Standard error -- TBST Tris-buffered saline with tween; depression -- pain -- anxiety -- inflammasome -- PKR -- hippocampus; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2019.05.025
• Languages: English
• ISSNs: 0306-4522

Abstract

Abstract: The chronic neuropathic pain-associated psychiatric disorders have seriously disturbed the quality of patients' life, such as depression and anxiety. Neuroinflammation in the hippocampus plays an important role in the neuropathic pain-associated depressive and anxiety disorders, but the underlying mechanism has not been thoroughly elucidated to date. The Nod-like receptor protein (NLRP)-1 inflammasome, which controls the production of pro-inflammatory cytokines, was broadly involved in the neuroinflammation-related diseases. In the present study, we show that the NLRP1 inflammasome is significantly activated in the hippocampus of rats subjected to the chronic constriction injury (CCI)-induced neuropathic pain. Inhibiting the product of NLRP1 inflammasome not only attenuated the depression-like behaviors but also suppressed the production of mature IL-1β in the hippocampus of CCI rats. The double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) has been recently shown to be a pivotal regulator for the activation of inflammasome. In the rats subjected to CCI neuropathic pain, the PKR was simultaneously activated in hippocampus. Functional inhibition of PKR suppressed the NLRP1 inflammasome activation and effectively attenuated the CCI-induced depression-like behaviors. These results indicate that the hippocampal PKR/NLRP1 inflammasome pathway play an important role in the development of the depressive behaviors after chronic neuropathic pain. Thus, interrupting this pathway might provide a novel therapeutic strategy for neuropathic pain-associated depressive disorders. Highlights: The NLRP1 inflammasome is activated in the hippocampus of CCI rats. Hippocampal PKR regulates the activation of NLRP1 inflammasome. The PKR/NLRP1 inflammasome pathway contributes to the depressive behaviors in CCI rats.