Depressive-like Behavior Is Accompanied by Prefrontal Cortical Innate Immune Fatigue and Dendritic Spine Losses after HIV-1 Tat and Morphine Exposure.
Depressive-like Behavior Is Accompanied by Prefrontal Cortical Innate Immune Fatigue and Dendritic Spine Losses after HIV-1 Tat and Morphine Exposure.
复制标题
DOI：
10.3390/v15030590
复制
发表时间：
2023-02-21
期刊：
影响因子：
--
通讯作者：
Hauser KF
中科院分区：
文献类型：
--
作者：
Nass SR;Hahn YK;Ohene-Nyako M;McLane VD;Damaj MI;Thacker LR 2nd;Knapp PE;Hauser KF
阿片类药物使用障碍 (OUD) 和艾滋病毒是共病流行病，会加剧抑郁症。 HIV 和病毒蛋白 Tat 可以直接诱导奖赏和情绪脑回路内的神经元损伤，包括前额皮质 (PFC)。这种损害涉及兴奋性毒性机制和通过神经炎症的更间接途径，这两种途径都可能因阿片类药物的共同暴露而恶化。为了评估兴奋性毒性和/或神经炎症是否可能导致 HIV 感染者 (PWH) 和使用阿片类药物的人出现抑郁行为，将雄性小鼠暴露于 HIV-1 Tat 八周，在最后两周内逐渐增加吗啡剂量，并评估抑郁样行为。 Tat 表达降低了蔗糖消耗和适应性，而吗啡给药则增加了食物消耗，并加剧了 Tat 诱导的筑巢和挖洞活动（与健康相关的活动）的减少。在所有治疗组中，抑郁样行为与 PFC 中促炎细胞因子的增加相关。然而，大多数促炎细胞因子不受 Tat 或吗啡影响，这支持了先天免疫反应适应长期 Tat 暴露的理论。此外，Tat 增加了 PFC 中抗炎细胞因子 IL-10 的水平，服用吗啡会加剧这种情况。 Tat（而不是吗啡）降低了前扣带回第五层锥体神经元的树突棘密度。总之，我们的研究结果表明，HIV-1 Tat 和吗啡会不同程度地诱发与前额皮质内神经炎症增加、突触损失和免疫疲劳相关的抑郁样行为。
Opioid use disorder (OUD) and HIV are comorbid epidemics that can increase depression. HIV and the viral protein Tat can directly induce neuronal injury within reward and emotionality brain circuitry, including the prefrontal cortex (PFC). Such damage involves both excitotoxic mechanisms and more indirect pathways through neuroinflammation, both of which can be worsened by opioid co-exposure. To assess whether excitotoxicity and/or neuroinflammation might drive depressive behaviors in persons infected with HIV (PWH) and those who use opioids, male mice were exposed to HIV-1 Tat for eight weeks, given escalating doses of morphine during the last two weeks, and assessed for depressive-like behavior. Tat expression decreased sucrose consumption and adaptability, whereas morphine administration increased chow consumption and exacerbated Tat-induced decreases in nesting and burrowing—activities associated with well-being. Across all treatment groups, depressive-like behavior correlated with increased proinflammatory cytokines in the PFC. Nevertheless, supporting the theory that innate immune responses adapt to chronic Tat exposure, most proinflammatory cytokines were unaffected by Tat or morphine. Further, Tat increased PFC levels of the anti-inflammatory cytokine IL-10, which were exacerbated by morphine administration. Tat, but not morphine, decreased dendritic spine density on layer V pyramidal neurons in the anterior cingulate. Together, our findings suggest that HIV-1 Tat and morphine differentially induce depressive-like behaviors associated with increased neuroinflammation, synaptic losses, and immune fatigue within the PFC.
登录
查看更多内容
DOI：
10.1097/qai.0b013e318229ba41
发表时间：
2011-10-01
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Byrd DA;Fellows RP;Morgello S;Franklin D;Heaton RK;Deutsch R;Atkinson JH;Clifford DB;Collier AC;Marra CM;Gelman B;McCutchan JA;Duarte NA;Simpson DM;McArthur J;Grant I;CHARTER Group
通讯作者：
CHARTER Group
影响因子：
3.8
作者：
Arango, JC;Simmonds, P;Bell, JE
通讯作者：
Bell, JE
趋化因子 CXCL1 及其受体 CXCR2 会导致小鼠慢性应激诱发的抑郁症。
影响因子：
4.8
作者：
Chai, Hui-Hui;Fu, Xiao-Chun;Li, Shao-Peng
通讯作者：
Li, Shao-Peng
DOI：
10.1007/s11481-021-09985-4
发表时间：
2022-06
期刊：
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
影响因子：
--
作者：
Cirino TJ;Alleyne AR;Duarte V;Figueroa A;Simons CA;Anceaume EM;Kendrick J;Wallman O;Eans SO;Stacy HM;Medina JM;McLaughlin JP
通讯作者：
McLaughlin JP
DOI：
10.1016/j.bpsc.2017.04.002
发表时间：
2017-10
期刊：
Biological psychiatry. Cognitive neuroscience and neuroimaging
影响因子：
--
作者：
McLaughlin JP;Paris JJ;Mintzopoulos D;Hymel KA;Kim JK;Cirino TJ;Gillis TE;Eans SO;Vitaliano GD;Medina JM;Krapf RC;Stacy HM;Kaufman MJ
通讯作者：
Kaufman MJ