Brooke S, Chan R, Howard S, Sapolsky R
Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9457-62. doi: 10.1073/pnas.94.17.9457.
HIV infection often involves the development of AIDS-related dementia complex, a variety of neurologic, neuropsychologic, and neuropathologic impairments. A possible contributor to AIDS-related dementia complex is the HIV envelope glycoprotein gp120, which damages neurons via a complex glutamate receptor- and calcium-dependent cascade. We demonstrate an endocrine modulation of the deleterious effects of gp120 in primary hippocampal and cortical cultures. Specifically, we observe that gp120-induced calcium mobilization and neurotoxicity are exacerbated by glucocorticoids, the adrenal steroids secreted during stress. Importantly, this deleterious synergy can occur between gp120 and synthetic glucocorticoids (such as prednisone or dexamethasone) that are used clinically in high concentrations to treat severe cases of the Pneumocystis carinii pneumonia typical of HIV infection. Conversely, we also observe that estradiol protects neurons from the deleterious actions of gp120, reducing toxicity and calcium mobilization.
HIV感染常常会引发与艾滋病相关的痴呆综合征，这是一种涉及多种神经、神经心理和神经病理损伤的病症。与艾滋病相关的痴呆综合征的一个可能成因是HIV包膜糖蛋白gp120，它通过一个复杂的、依赖谷氨酸受体和钙的级联反应来损害神经元。我们在原代海马体和皮质培养物中证明了内分泌对gp120有害作用的调节。具体而言，我们观察到糖皮质激素（应激期间分泌的肾上腺类固醇）会加剧gp120诱导的钙动员和神经毒性。重要的是，gp120与临床上用于高浓度治疗典型HIV感染的卡氏肺孢子虫肺炎严重病例的合成糖皮质激素（如泼尼松或地塞米松）之间可能会出现这种有害的协同作用。相反，我们还观察到雌二醇可保护神经元免受gp120的有害作用，降低毒性和钙动员。
