Gaspar Jessica C, Healy Catherine, Ferdousi Mehnaz I, Roche Michelle, Finn David P
Pharmacology and Therapeutics, National University of Ireland Galway, H91 W5P7 Galway, Ireland.
Galway Neuroscience Centre, National University of Ireland Galway, H91 W5P7 Galway, Ireland.
Biomedicines. 2021 May 27;9(6):610. doi: 10.3390/biomedicines9060610.
Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that exist in three isoforms: PPARα, PPARβ/δ and PPARγ. Studies suggest that the PPAR signalling system may modulate pain, anxiety and cognition. The aim of the present study was to investigate whether endogenous signalling via PPARs differentially modulates innate anxiety responses and mnemonic function in the presence and absence of inflammatory pain. We examined the effects of intraperitoneal administration of GW6471 (PPARα antagonist), GSK0660 (PPARβ/δ antagonist), GW9662 (PPARγ antagonist), and -palmitoylethanolamide (PEA) on rat behaviour in the elevated plus maze (EPM), open field (OF), light-dark box (LDB), and novel object recognition (NOR) tests in the presence or absence of chronic inflammatory pain. Complete Freund's Adjuvant (CFA)-injected rats exhibited impaired recognition and spatial mnemonic performance in the NOR test and pharmacological blockade of PPARα further impaired spatial memory in CFA-treated rats. -oleoylethanolamide (OEA) levels were higher in the dorsal hippocampus in CFA-injected animals compared to their counterparts. The results suggest a modulatory effect of CFA-induced chronic inflammatory pain on cognitive processing, but not on innate anxiety-related responses. Increased OEA-PPARα signalling may act as a compensatory mechanism to preserve spatial memory function following CFA injection.
过氧化物酶体增殖物激活受体（PPARs）是配体依赖性转录因子，存在三种亚型：PPARα、PPARβ/δ和PPARγ。研究表明，PPAR信号系统可能调节疼痛、焦虑和认知。本研究的目的是调查在存在和不存在炎性疼痛的情况下，通过PPARs的内源性信号是否差异调节先天性焦虑反应和记忆功能。我们在慢性炎性疼痛存在或不存在的情况下，检查了腹腔注射GW6471（PPARα拮抗剂）、GSK0660（PPARβ/δ拮抗剂）、GW9662（PPARγ拮抗剂）和棕榈酰乙醇胺（PEA）对大鼠在高架十字迷宫（EPM）、旷场试验（OF）、明暗箱（LDB）和新物体识别（NOR）试验中的行为的影响。注射完全弗氏佐剂（CFA）的大鼠在NOR试验中表现出识别和空间记忆性能受损，PPARα的药理阻断进一步损害了CFA处理大鼠的空间记忆。与未注射CFA的动物相比，注射CFA的动物背侧海马中的油酰乙醇胺（OEA）水平更高。结果表明，CFA诱导的慢性炎性疼痛对认知加工有调节作用，但对先天性焦虑相关反应没有调节作用。OEA-PPARα信号增加可能作为一种补偿机制，以在注射CFA后保留空间记忆功能。
