Cognitive and Neural Science Program, Department of Psychology, University of South Carolina, Columbia, SC 29208, United States of America.
Cognitive and Neural Science Program, Department of Psychology, University of South Carolina, Columbia, SC 29208, United States of America.
Exp Neurol. 2022 Nov;357:114174. doi: 10.1016/j.expneurol.2022.114174. Epub 2022 Jul 18.
Individuals living with human immunodeficiency virus type 1 (HIV-1) exhibit an increased prevalence of neuropsychiatric comorbities (e.g., apathy) relative to their seronegative counterparts. Given the profound functional consequences associated with apathy, characterizing the multidimensional neuropsychiatric syndrome, and associated neural mechanisms, following chronic HIV-1 viral protein exposure remains a critical need. HIV-1-associated apathy was examined by quantifying goal-directed behaviors, indexed using voluntary wheel running, during the diurnal and nocturnal cycle. Apathetic behaviors in the HIV-1 transgenic (Tg) rat were characterized by a profound decrease in the number of running bouts during both the diurnal and nocturnal cycle, supporting a prominent deficit in the self-initiation of spontaneous behaviors. Additionally, HIV-1 Tg animals exhibited a decreased reinforcing efficacy of voluntary wheel running during the nocturnal cycle. Following the completion of voluntary wheel running, synaptic dysfunction in medium spiny neurons (MSNs) of the nucleus accumbens core (NAcc) was examined as a potential neural mechanism underlying HIV-1-associated apathy. HIV-1 Tg animals displayed prominent synaptic dysfunction in MSNs of the NAcc, characterized by enhanced dendritic branching complexity and a population shift towards an immature dendritic spine phenotype relative to control animals. Synaptic dysfunction, which accounted for 42.0% to 68.5% of the variance in the number of running bouts, was strongly associated with the self-initiation of spontaneous behaviors. Establishment of the relationship between synaptic dysfunction and apathy affords a key target for the development of novel therapeutics and cure strategies for affective alterations associated with HIV-1.
个体携带人类免疫缺陷病毒 1 型（HIV-1）时，与血清阴性个体相比，表现出更高的神经精神合并症（如冷漠）发生率。鉴于冷漠与深刻的功能后果相关，描述多维神经精神综合征及其相关的神经机制，仍然是慢性 HIV-1 病毒蛋白暴露后需要解决的关键问题。通过量化目标导向行为（使用自愿轮跑来衡量），来研究 HIV-1 相关性冷漠。HIV-1 转基因（Tg）大鼠的冷漠行为表现为昼夜周期中跑步次数的显著减少，这表明自主行为的启动存在明显缺陷。此外，HIV-1 Tg 动物在夜间周期中自愿轮跑的强化效果降低。完成自愿轮跑后，检查伏隔核核心（NAcc）中的中脑多巴胺神经元（MSNs）的突触功能障碍，作为 HIV-1 相关性冷漠的潜在神经机制。HIV-1 Tg 动物的 NAcc 中的 MSNs 表现出明显的突触功能障碍，其特征为树突分支复杂性增强，以及向不成熟的树突棘表型的群体转移，与对照动物相比。突触功能障碍占跑步次数变化的 42.0%至 68.5%，与自主行为的启动密切相关。建立突触功能障碍与冷漠之间的关系，为开发与 HIV-1 相关的情感改变的新型治疗方法和治愈策略提供了关键目标。
