Nicotine attenuates the effect of HIV-1 proteins on the neural circuits of working and contextual memories.
Nicotine attenuates the effect of HIV-1 proteins on the neural circuits of working and contextual memories.
复制标题
DOI：
10.1186/s13041-015-0134-x
复制
发表时间：
2015-07-24
期刊：
影响因子：
3.6
通讯作者：
Li MD
中科院分区：
文献类型：
--
作者：
Nesil T;Cao J;Yang Z;Chang SL;Li MD
人类免疫缺陷病毒(HIV)-1相关性神经认知障碍(HAND)以突触损伤和脑内神经元丢失为特征。谷氨酸能传递过度和胆碱能神经元丢失是手的主要指标。尼古丁作为胆碱能通道调节剂，其在神经退行性疾病和认知障碍中的认知增强作用已被证明。然而，目前尚不清楚尼古丁是否对记忆和手部突触的可塑性形成有任何积极影响。我们研究了尼古丁对HIV-1转基因大鼠(TG)和F344对照组大鼠突触可塑性和海马-前额叶皮质(PFC)-杏仁核依赖记忆形成的影响。长期尼古丁治疗(0.4 mg/kg，基础，皮下)显著减轻HIV-1TG大鼠在空间和情境恐惧记忆中的认知缺陷，但损害F344大鼠的情境学习记忆。为了确定尼古丁在HIV-1蛋白引起的突触功能障碍中的作用，我们使用定制的qRT-PCR阵列分析了与突触可塑性相关的关键代表基因在HIV-1TG和F344大鼠的海马区、前额叶和杏仁核中的表达。HIV-1蛋白以脑区特异性的方式显著改变了谷氨酸受体介导的细胞内钙级联及其下游信号级联。此外，长期尼古丁治疗逆转了HIV-1蛋白对参与突触可塑性的三个脑区基因表达的影响。尼古丁对HIV-1TG和F344大鼠的影响有显著差异。我们的发现表明，尼古丁可以减弱HIV病毒蛋白对认知功能的影响，并对参与突触可塑性和记忆形成的细胞内信号级联产生脑区和菌株特异性的影响。本文的在线版本(doi：10.1186/s13041-0150134-x)包含补充材料，授权用户可以使用。
Human immunodeficiency virus (HIV)-1-associated neurocognitive disorders (HAND) are characterized by synaptic damage and neuronal loss in the brain. Excessive glutamatergic transmission and loss of cholinergic neurons are the major indicators of HAND. Nicotine acts as a cholinergic channel modulator, and its cognitive-enhancing effect in neurodegenerative and cognitive disorders has been documented. However, it is unclear whether nicotine has any positive effect on memory and synaptic plasticity formation in HAND. We investigated the effects of nicotine on synaptic plasticity and hippocampus–prefrontal cortex (PFC)–amygdala-dependent memory formation in the HIV-1 transgenic (Tg) and F344 control rats. Chronic nicotine treatment (0.4 mg/kg nicotine, base, subcutaneously) significantly attenuated the cognitive deficits in the HIV-1Tg rats in both the spatial and contextual fear memories but impaired the contextual learning memory in the F344 rats. To determine the role of nicotine in the synaptic dysfunction caused by HIV-1 proteins, we analyzed the expression of key representative genes related to synaptic plasticity in the hippocampus, PFC, and amygdala of the HIV-1Tg and F344 rats using a custom-designed qRT-PCR array. The HIV-1 proteins significantly altered the glutamate receptor-mediated intracellular calcium cascade and its downstream signaling cascade in a brain region-specific manner. Further, chronic nicotine treatment reversed the effect of HIV-1 proteins on the expression of genes involved in synaptic plasticity in the three brain regions. The effects of nicotine differed significantly in the HIV-1Tg and F344 rats. Our findings indicate that nicotine can attenuate the effect of HIV viral proteins on cognitive function and produce a brain region- and strain-specific effect on the intracellular signaling cascades involved in synaptic plasticity and memory formation. The online version of this article (doi:10.1186/s13041-015-0134-x) contains supplementary material, which is available to authorized users.