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Flannery, LE,Henry, RJ,Kerr, DM,Finn, DP,Roche, M
2018
June
Journal Of Neuroscience Research
FAAH, but not MAGL, inhibition modulates acute TLR3-induced neuroimmune signaling in the rat, independent of sex
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neuroimmune TLR viral hypothalamus cannabinoid POLYINOSINIC-POLYCYTIDYLIC ACID ACUTE POSTOPERATIVE PAIN TUMOR-NECROSIS-FACTOR SICKNESS BEHAVIOR GENDER-DIFFERENCES INNATE IMMUNE FEMALE RATS PHARMACOLOGICAL INHIBITION CANNABINOID RECEPTOR CYTOKINE SECRETION
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Toll-like receptor (TLR)3 is a key component of the innate immune response to viral infection. The present study firstly examined whether sex differences exist in TLR3-induced inflammatory, endocrine, and sickness responses. The data revealed that TLR3-induced expression of interferon- or NFkB-inducible genes (IFN-/, IP-10, or TNF-), either peripherally (spleen) or centrally (hypothalamus), did not differ between male and female rats, with the exception of TLR3-induced IFN- expression in the spleen of female, but not male, rats 8 hr post TLR3 activation. Furthermore, TLR3 activation increased plasma corticosterone levels, induced fever, and reduced locomotor activity and body weight effects independent of sex. Thus, the acute-phase inflammatory, endocrine, and sickness responses to TLR3 activation exhibit minimal sex-related differences. A further aim of this study was to examine whether enhancing endocannabinoid tone namely, 2-arachidonylglycerol (2-AG) or N-arachidonoylethanolamine (AEA), exhibited similar effects on TLR3-induced inflammatory responses in male versus female rats. Systemic administration of the monoacylglycerol lipase (MAGL) inhibitor MJN110 and subsequent increases in 2-AG levels did not alter the TLR3-induced increase in IP-10, IRF7, or TNF- expression in the spleen or the hypothalamus of male or female rats. In contrast, the fatty acid amide hydrolase (FAAH) inhibitor URB597 increased levels of AEA and related N-acylethanolamines, an effect associated with the attenuation of TLR3-induced inflammatory responses in the hypothalamus, but not the spleen, of male and female rats. These data support a role for FAAH, but not MAGL, substrates in the modulation of TLR3-induced neuroinflammatory responses, effects independent of sex.
10.1002/jnr.24120
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