Cocaine Regulates NLRP3 Inflammasome Activity and CRF Signaling in a Region- and Sex-Dependent Manner in Rat Brain.
Cocaine Regulates NLRP3 Inflammasome Activity and CRF Signaling in a Region- and Sex-Dependent Manner in Rat Brain.
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DOI：
10.3390/biomedicines11071800
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发表时间：
2023-06-23
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
可卡因是世界上滥用最多的药物之一，能够在体外和体内激活小胶质细胞。几种神经免疫途径已被认为在可卡因介导的小胶质细胞活化中发挥作用。先前的研究表明，可卡因以区域特异性的方式激活自我给药小鼠大脑中的小胶质细胞。为了进一步表征可卡因对体内小胶质细胞和神经免疫信号传导的影响，我们利用可卡因自身给药的远交系大鼠的两种性别的大脑来探索纹状体和海马（HP）中小胶质细胞的活化状态、含NOD-、LRR-和pyrin结构域的蛋白3（NLRP 3）炎性小体活性、促肾上腺皮质激素释放因子（CRF）信号传导和NF-κB水平。将相同性别的配对大鼠（未给药）作为对照。我们的研究结果表明，可卡因增加了两种性别的纹状体和HP的神经炎症，男性大脑中的增加相对较高。在纹状体，可卡因上调NLRP 3炎性小体活性和CRF水平的男性，但不是在女性。与此相反，可卡因增加NLRP 3炎性小体活性的HP的女性，但不是在男性，并没有影响CRF信号在这一地区的任何性别。有趣的是，可卡因增加纹状体和HP中的NF-κB水平，没有性别差异。总之，我们的研究结果提供了证据表明，可卡因可以发挥区域和性别特异性差异的神经免疫信号在大脑中。靶向神经免疫信号已被建议作为可卡因使用障碍（CUD）的可能治疗方法。我们目前的研究结果表明，在确定这些新的治疗方法的疗效时，应考虑性别。
Cocaine, one of the most abused drugs worldwide, is capable of activating microglia in vitro and in vivo. Several neuroimmune pathways have been suggested to play roles in cocaine-mediated microglial activation. Previous work showed that cocaine activates microglia in a region-specific manner in the brains of self-administered mice. To further characterize the effects of cocaine on microglia and neuroimmune signaling in vivo, we utilized the brains from both sexes of outbred rats with cocaine self-administration to explore the activation status of microglia, NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activity, corticotropin-releasing factor (CRF) signaling, and NF-κB levels in the striatum and hippocampus (HP). Age-matched rats of the same sex (drug naïve) served as controls. Our results showed that cocaine increased neuroinflammation in the striatum and HP of both sexes with a relatively higher increases in male brains. In the striatum, cocaine upregulated NLRP3 inflammasome activity and CRF levels in males but not in females. In contrast, cocaine increased NLRP3 inflammasome activity in the HP of females but not in males, and no effects on CRF signaling were observed in this region of either sex. Interestingly, cocaine increased NF-κB levels in the striatum and HP with no sex difference. Taken together, our results provide evidence that cocaine can exert region- and sex-specific differences in neuroimmune signaling in the brain. Targeting neuroimmune signaling has been suggested as possible treatment for cocaine use disorders (CUDs). Our current results indicate that sex should be taken into consideration when determining the efficacy of these new therapeutic approaches.
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影响因子：
4.2
作者：
Bachtell RK;Jones JD;Heinzerling KG;Beardsley PM;Comer SD
通讯作者：
Comer SD
影响因子：
5.1
作者：
Gutzeit O;Segal L;Korin B;Iluz R;Khatib N;Dabbah-Assadi F;Ginsberg Y;Fainaru O;Ross MG;Weiner Z;Beloosesky R
通讯作者：
Beloosesky R
DOI：
10.1073/pnas.0504438102
发表时间：
2005-08-09
影响因子：
11.1
作者：
Ahmed, SH;Lutjens, R;Sanna, PP
通讯作者：
Sanna, PP
影响因子：
8.8
作者：
Guneykaya, Dilansu;Ivanov, Andranik;Wolf, Susanne A.
通讯作者：
Wolf, Susanne A.
影响因子：
3.4
作者：
Carrette, Lieselot L. G.;de Guglielmo, Giordano;Geprge, Olivier
通讯作者：
Geprge, Olivier