Physiological Corticosterone Attenuates gp120-Mediated Microglial Activation and Is Associated with Reduced Anxiety-Like Behavior in gp120-Expressing Mice.
Physiological Corticosterone Attenuates gp120-Mediated Microglial Activation and Is Associated with Reduced Anxiety-Like Behavior in gp120-Expressing Mice.
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DOI：
10.3390/v15020424
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发表时间：
2023-02-02
期刊：
影响因子：
--
通讯作者：
Paris JJ
中科院分区：
文献类型：
--
作者：
Moss EM;Mahdi F;Worth CJ;Paris JJ
尽管联合抗逆转录病毒疗法(CART)有好处，但在中枢神经系统内仍可检测到具有病毒毒性的HIV蛋白。接受CART治疗的患者中，大约有一半患有神经损伤。这些效应背后的机制可能涉及到具有病毒毒性的HIV蛋白，包括糖蛋白120(Gp120)。糖蛋白-120因其激活小胶质细胞的能力而具有神经毒性。皮质酮在体外被发现可以减轻由gp120诱导的小胶质细胞因子产生引起的神经元死亡。然而，皮质酮对小胶质细胞激活状态和相关行为结果的浓度依赖性影响尚不清楚。在此，我们进行了平行的体外和体内研究，以评估gp120介导的对小胶质细胞激活、运动功能、焦虑和抑郁样行为的影响，以及皮质酮减弱这些影响的能力。我们发现gp120在体外激活了小胶质细胞，皮质酮在100 nM的最佳浓度下减弱了这一作用。表达gp120的转基因小鼠在高架+迷宫中表现出更多的焦虑样行为，并且更长的gp120暴露时间与运动障碍和焦虑样行为有关。在表达gp120的男性和发情期女性中，循环皮质酮水平较低。循环中的皮质酮水平越高，焦虑样行为就越少。这些发现可能表明糖皮质激素有能力减轻gp120介导的神经炎症和焦虑样行为。
Despite the benefits of combinatorial antiretroviral therapies (cART), virotoxic HIV proteins are still detectable within the central nervous system. Approximately half of all cART-treated patients contend with neurological impairments. The mechanisms underlying these effects likely involve virotoxic HIV proteins, including glycoprotein 120 (gp120). Glycoprotein-120 is neurotoxic due to its capacity to activate microglia. Corticosterone has been found to attenuate neuronal death caused by gp120-induced microglial cytokine production in vitro. However, the concentration-dependent effects of corticosterone on microglial activation states and the associated behavioral outcomes are unclear. Herein, we conducted parallel in vitro and in vivo studies to assess gp120-mediated effects on microglial activation, motor function, anxiety- and depression-like behavior, and corticosterone’s capacity to attenuate these effects. We found that gp120 activated microglia in vitro, and corticosterone attenuated this effect at an optimal concentration of 100 nM. Transgenic mice expressing gp120 demonstrated greater anxiety-like behavior on an elevated plus maze, and a greater duration of gp120 exposure was associated with motor deficits and anxiety-like behavior. Circulating corticosterone was lower in gp120-expressing males and diestrous females. Greater circulating corticosterone was associated with reduced anxiety-like behavior. These findings may demonstrate a capacity for glucocorticoids to attenuate gp120-mediated neuroinflammation and anxiety-like behavior.
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DOI：
10.1016/j.bbi.2016.01.020
发表时间：
2016-05
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Bachis A;Forcelli P;Masliah E;Campbell L;Mocchetti I
通讯作者：
Mocchetti I
影响因子：
6.2
作者：
Podhaizer, Elizabeth M.;Zou, Shiping;Fitting, Sylvia;Samano, Kimberly L.;El-Hage, Nazira;Knapp, Pamela E.;Hauser, Kurt F.
通讯作者：
Hauser, Kurt F.
HIV-1 病毒粒子相关蛋白 vpr 是人类糖皮质激素受体的共激活剂。
影响因子：
15.3
作者：
Kino, T;Gragerov, A;Kopp, J B;Stauber, R H;Pavlakis, G N;Chrousos, G P
通讯作者：
Chrousos, G P
影响因子：
4.1
作者：
Coutinho, Agnes E.;Chapman, Karen E.
通讯作者：
Chapman, Karen E.
影响因子：
5.3
作者：
Hoefer, Melanie M.;Sanchez, Ana B.;Maung, Ricky;de Rozieres, Cyrus M.;Catalan, Irene C.;Dowling, Cari C.;Thaney, Victoria E.;Pina-Crespo, Juan;Zhang, Dongxian;Roberts, Amanda J.;Kaul, Marcus
通讯作者：
Kaul, Marcus