Yao Honghong, Bethel-Brown Crystal, Buch Shilpa
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160.
Am J Infect Dis. 2009 Jan 1;5(1):26-30. doi: 10.3844/ajidsp.2009.26.30.
While it has been well documented that drugs of abuse such as cocaine can cause enhanced progression of HIV-Associated Neuropathological Disorders (HAND), the underlying mechanisms mediating these effects remain poorly understood. In the present study, we explored the impact of cocaine exposure (I μM and 10 μM) on the dendritic beading in rat primary hippocampal neurons. Using the approach of transfection with green fluorescent protein, we observed significant dendritic swelling in hippocampal neurons exposed to 10 μM but not 1 μM of cocaine when compared with the saline treated group. Cocaine exposure also resulted in decreased expression of the synaptic plasticity gene, Arc as evidenced by Western blotting. Intriguingly, cocaine exposure of primary neurons in the presence of the neurotoxin-HIV envelope protein gp 120, resulted in increased enhancement of neuronal beading as compared with exposure of neurons to either agent alone. Taken together these findings imply that cocaine in co-operation with HIV protein exacerbates neuronal damage in the brains of HIV-infected cocaine abusers.
虽然已有充分文献记载,可卡因等滥用药物会导致与HIV相关的神经病理障碍(HAND)病情加速发展,但其介导这些效应的潜在机制仍知之甚少。在本研究中,我们探究了可卡因暴露(1 μM和10 μM)对大鼠原代海马神经元树突串珠形成的影响。采用绿色荧光蛋白转染方法,我们观察到,与生理盐水处理组相比,暴露于10 μM而非1 μM可卡因的海马神经元出现了明显的树突肿胀。蛋白质印迹法证实,可卡因暴露还导致突触可塑性基因Arc的表达降低。有趣的是,与单独将神经元暴露于任一药物相比,在存在神经毒素HIV包膜蛋白gp 120的情况下,原代神经元暴露于可卡因会导致神经元串珠形成增强。综合这些发现表明,可卡因与HIV蛋白协同作用会加剧HIV感染的可卡因滥用者大脑中的神经元损伤。