Iyer A M, Brooke S M, Sapolsky R M
Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
Brain Res. 1998 Oct 19;808(2):305-9. doi: 10.1016/s0006-8993(98)00819-1.
A significant subset of HIV-positive patients suffer from AIDS-Related Dementia Complex (ADC), an array of neurologic and neuropsychologic impairments. The HIV coat protein gp120 has been implicated in the deleterious neurologic consequences of HIV infection, damaging neurons through a glutamatergic and calcium-dependent pathway. We have previously reported that glucocorticoids, the adrenal steroids secreted during stress, can exacerbate the neurotoxic and calcium-mobilizing effects of gp120 in hippocampal and cortical cultures. Because both the symptomatology of ADC, as well as the neuropathologic profile of post-mortem HIV brains suggests an involvement of the striatum, we examined whether glucocorticoids could also augment the damaging effects of gp120 in primary striatal cultures. We observe that neither gp120 nor the glucocorticoid corticosterone, when administered alone, cause neurotoxicity or mobilization of free cytosolic calcium; however, a combination of the two caused significant toxicity and neuron death. This, along with our prior findings of gp120-glucocorticoid interactions, is striking, given the heavy clinical use of synthetic glucocorticoids for management of pulmonary complications of HIV infection.
相当一部分HIV阳性患者患有艾滋病相关痴呆综合征（ADC），这是一系列神经和神经心理损伤。HIV外壳蛋白gp120与HIV感染的有害神经后果有关，它通过谷氨酸能和钙依赖途径损害神经元。我们之前曾报道，应激期间分泌的肾上腺类固醇糖皮质激素可加剧gp120在海马体和皮质培养物中的神经毒性和钙动员作用。由于ADC的症状以及死后HIV感染大脑的神经病理学特征均表明纹状体受累，因此我们研究了糖皮质激素是否也会增强gp120在原代纹状体培养物中的破坏作用。我们观察到，单独给予gp120或糖皮质激素皮质酮均不会引起神经毒性或游离胞浆钙的动员；然而，两者联合使用会导致明显的毒性和神经元死亡。考虑到合成糖皮质激素在临床上大量用于治疗HIV感染的肺部并发症，这一结果以及我们之前关于gp120 - 糖皮质激素相互作用的发现令人震惊。
