Network analysis of hippocampal neurons by microelectrode array in the presence of HIV-1 Tat and cocaine.
Network analysis of hippocampal neurons by microelectrode array in the presence of HIV-1 Tat and cocaine.
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DOI：
10.1002/jcp.26322
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发表时间：
2018-12
影响因子：
5.6
通讯作者：
Gordon J
中科院分区：
文献类型：
--
作者：
Mohseni Ahooyi T;Shekarabi M;Decoppet EA;Langford D;Khalili K;Gordon J
影响超过 30% 患者的 HIV 相关神经认知障碍是由中枢神经系统 HIV-1 感染引起的，部分包括病毒转录反式激活因子 Tat 蛋白的神经毒性作用。除了增加感染 HIV 的风险外，可卡因滥用还会增强 HIV-1 的神经病理影响。为了研究 Tat 和可卡因对海马神经元网络的干扰结果，采用微电极阵列开发了一个系统框架来评估培养的海马神经元的等级互相关系数。 Tat 和可卡因通过增强抑制性神经传递，对海马神经元网络内的神经元尖峰速率、幅度、同步活动和振荡产生不同程度的干扰。 Tat 介导的神经元尖峰损伤可通过去除 Tat 来逆转，从而恢复神经元活动。与神经元网络共培养的星形胶质细胞的存在减弱了 Tat 和可卡因对神经元功能的影响，表明星形胶质细胞在稳定神经元行为和增加神经元自发活动（如爆发幅度、频率和波传播速率）方面发挥着作用。总而言之，我们的研究表明，HIV 蛋白 Tat 和可卡因会损害海马神经元网络功能，而星形胶质细胞的存在会减轻网络功能障碍，这表明新发现的中枢神经系统中通过神经元-胶质细胞串扰维持离子稳态的途径。
HIV-associated neurocognitive disorders affecting greater than 30% of patients are caused by HIV-1 infection of the CNS, and in part, include neurotoxic effects of the viral transactivator of transcription, Tat protein. In addition to increasing the risk for becoming HIV infected, cocaine abuse enhances the neuropathogenic impacts of HIV-1. To investigate the outcome of Tat and cocaine interference in the hippocampal neuronal network, microelectrode arrays were employed to develop a systematic framework to assess the rank-cross-correlation coefficient in cultured hippocampal neurons. Tat and cocaine differentially disturbed neuronal spiking rates, amplitude, synchronous activity and oscillations within the hippocampal neuronal network via potentiation of inhibitory neurotransmission. The Tat-mediated impairment of neuronal spiking was reversible by removal of Tat, which restored neuronal activity. The presence of astrocytes co-cultured with neuronal networks diminished the effects of Tat and cocaine on neuron function suggesting a role for astrocytes in stabilizing neuronal behavior and increasing neuronal spontaneous activities such as bursting amplitude, frequency and wave propagation rate. Taken together, our studies indicate that the HIV protein Tat and cocaine impair hippocampal neuronal network functioning and that the presence of astrocytes alleviates network dysfunction pointing to a newly discovered pathway through which ionic homeostasis is maintained by neuron-glial crosstalk in the CNS.
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