Impact on Cortical Function of Cocaine Abuse Co-Occurring with HIV.
Impact on Cortical Function of Cocaine Abuse Co-Occurring with HIV.
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与艾滋病毒同时发生的可卡因滥用对皮质功能的影响。
DOI：
10.1038/npp.2016.222
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Napier,TCeleste
中科院分区：
文献类型：
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作者：
Napier,TCeleste
根据美国疾病控制中心（http：//www. CDC.目前有超过3600万人感染艾滋病毒，美国每年诊断出44000例新感染，通常反映了危险的性行为。药物使用障碍对艾滋病毒/艾滋病危机的每个阶段都有负面影响，药物使用障碍是防治这一全球流行病的主要障碍。除大麻外，可卡因是艾滋病毒成人中最常滥用的非法药物（例如，Martin等人，2016年）。可卡因的使用与从事危险性行为的可能性增加、疾病进展加速和不依从抗逆转录病毒治疗有关。对这种联系的一种新的解释与冲动的决策有关。虽然可卡因滥用者和艾滋病毒感染者在认知冲动性任务中的得分通常较高，但患有合并症的人往往表现出最大的冲动性（例如，Martin等人，2016年及其参考文献）。人类成像研究指出，这些缺陷会导致前额叶-皮质下网络受损（例如，米德等人，2011）。为了获得一个更机械的观点，并帮助确定潜在的治疗目标，我的实验室最近开始评估神经病理生理学内侧前额叶皮层（mPFC）的背景下，艾滋病毒/艾滋病合并症。我们专注于主要的输出，即锥体神经元。正如我们最近所综述的（Wayman et al，2015），我们的初步研究表明，急性暴露于一种突出的HIV-1神经毒性蛋白达特可诱导持久的mPFC星形胶质细胞增生和mPFC锥体神经元的过度兴奋性，慢性可卡因暴露会加剧这种情况。这些作用是由高电压激活的L型钙通道的过度激活介导的，并与Tat诱导的钙通道孔形成蛋白Cav 1表达增加有关。2-α1c。为了更好地将这一现象推广到大脑暴露于HIV-1蛋白的慢性性质，我们随后评估了可卡因自我给药后HIV-1转基因大鼠的mPFC病理生理学。正如Tat介导的兴奋性毒性所预测的那样，转基因大鼠表现出增强的mPFC Cav 1。2-α1c表达以及锥体细胞过度兴奋性和兴奋性毒性（Wesley et al，2016）。
According to the USA Center for Disease Control (http://www. cdc. gov/) over 36 million humans are currently living with HIV infection, with 44 000 new infections diagnosed annually in the USA, often reflecting risky sexual behavior. Substance use disorders (SUD) negatively influence every stage of the HIV/AIDS crisis, and SUD are a major obstacle in combating this global pandemic. Other than marijuana, cocaine is the most frequently abused illicit drug in HIV adults (eg, Martin et al., 2016). Cocaine use is associated with increased likelihood of engaging in risky sex, accelerated disease progression, and non-adherence to antiretroviral treatment. An emerging explanation for this association relates to impulsive decision-making. While both cocaine-abusing and HIV-infected individuals often score higher on cognitive impulsivity tasks, those with the comorbidity tend to show the greatest impulsivity (eg, Martin et al, 2016 and references therein). Human imaging studies point to impairments in prefrontal–subcortical networks in these deficits (eg, Meade et al, 2011). To capture a more mechanistic view and to help identify potential therapeutic targets, my laboratory recently set out to evaluate neuropathophysiology within the medial prefrontal cortex (mPFC) in the context of HIV/AIDS comorbidity. We focused on the principal outputs, ie, pyramidal neurons. As we recently reviewed (Wayman et al, 2015), our initial studies demonstrated that acute exposure to a prominent HIV-1 neurotoxic protein, Tat, induced an enduring mPFC astrogliosis and hyper excitability of mPFC pyramidal neurons that was exacerbated by chronic cocaine exposure. These effects were mediated by overactivation of high-voltage-activated L-type calcium channels and were associated with a Tat-induced increase expression of a calcium channel poreforming protein, Cav1. 2-α1c. To better generalize the phenomenon to the chronic nature of brain exposure to HIV-1 proteins, we subsequently evaluated mPFC pathophysiology in HIV-1 transgenic rats following cocaine self-administration. As predicted by Tat-mediated excitotoxicity, the transgenic rats exhibited enhanced mPFC Cav1. 2-α1c expression, and a pyramidal cell hyper excitability and excitotoxicity (Wesley et al, 2016).