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表达 HIV-1 包膜蛋白 gp120 的转基因小鼠中转录因子 NF-κB 的改变对甲基苯丙胺诱导的刻板行为的影响。

Alteration of Methamphetamine-induced stereotypic behaviour in transgenic mice expressing HIV-1 envelope protein gp120.

机构信息

Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 N. Torrey Pines Road, SV142 La Jolla, CA 92037, USA.

出版信息

J Neurosci Methods. 2010 Feb 15;186(2):222-5. doi: 10.1016/j.jneumeth.2009.11.007. Epub 2009 Nov 13.

Abstract

The use of drugs for recreational purposes, in particular Methamphetamine, is associated with an increased risk of infection with human immunodeficiency virus (HIV)-1. HIV-1 infection in turn can lead to HIV-associated neurological disorders (HAND) that range from mild cognitive and motor impairment to HIV-associated dementia (HAD). Interestingly, post mortem brain specimens from HAD patients and transgenic (tg) mice expressing the viral envelope protein gp120 in the central nervous system display similar neuropathological signs. In HIV patients, the use of Methamphetamine appears to aggravate neurocognitive alterations. In the present study, we injected HIV/gp120tg mice and non-transgenic littermate control animals with Methamphetamine dissolved in Saline or Saline vehicle and assessed locomotion and stereotyped behaviour. We found that HIVgp120-transgenic mice differ significantly from non-transgenic controls in certain domains of their behavioural response to Methamphetamine. Thus this experimental model system may be useful to further study the mechanistic interaction of both the viral envelope protein and the psychostimulant drug in behavioural alterations and neurodegenerative disease.

摘要

出于娱乐目的而使用毒品,特别是冰毒,会增加感染人类免疫缺陷病毒(HIV-1)的风险。反过来,HIV-1 感染会导致与 HIV 相关的神经障碍(HAND),其范围从轻度认知和运动障碍到 HIV 相关痴呆(HAD)。有趣的是,HAD 患者的死后脑组织标本和在中枢神经系统中表达病毒包膜蛋白 gp120 的转基因(tg)小鼠显示出类似的神经病理学迹象。在 HIV 患者中,冰毒的使用似乎会加重神经认知改变。在本研究中,我们给 HIV/gp120tg 小鼠和非转基因同窝对照动物注射溶解在生理盐水中的冰毒或生理盐水载体,并评估运动和刻板行为。我们发现,HIVgp120 转基因小鼠在对冰毒的行为反应的某些方面与非转基因对照有显著差异。因此,这种实验模型系统可能有助于进一步研究病毒包膜蛋白和精神兴奋剂药物在行为改变和神经退行性疾病中的机械相互作用。

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