Combination of methamphetamine and HIV-1 gp120 causes distinct long-term alterations of behavior, gene expression, and injury in the central nervous system.
Combination of methamphetamine and HIV-1 gp120 causes distinct long-term alterations of behavior, gene expression, and injury in the central nervous system.
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DOI：
10.1016/j.expneurol.2014.09.010
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发表时间：
2015-01
影响因子：
5.3
通讯作者：
Kaul, Marcus
中科院分区：
文献类型：
--
作者：
Hoefer, Melanie M.;Sanchez, Ana B.;Maung, Ricky;de Rozieres, Cyrus M.;Catalan, Irene C.;Dowling, Cari C.;Thaney, Victoria E.;Pina-Crespo, Juan;Zhang, Dongxian;Roberts, Amanda J.;Kaul, Marcus
关键词：
甲基苯丙胺(甲基苯丙胺)滥用在感染人类免疫缺陷病毒1型(HIV-1)的个人中经常发生，并被怀疑会加剧艾滋病毒相关的神经认知障碍(HAND)。冰毒是一种精神刺激剂，会损害几个神经递质系统，艾滋病毒蛋白会引发神经元损伤，但病毒感染和冰毒滥用的综合影响尚不完全清楚。在这项研究中，我们对3-4个月大的表达HIV包膜蛋白gp120的转基因小鼠(HIV/gp120tg)进行了递增剂量、多次暴食的冰毒治疗。在戒毒6~7个月后进行行为测试和神经病理、电生理及基因表达分析，分析其远期疗效。行为学测试表明，用冰毒治疗的HIV/gp120tg和WT动物都表现出学习和记忆障碍。神经病理学分析显示，类似于HIV/gp120的冰毒导致WT动物海马区和大脑皮层神经元树突和突触前终末明显丢失。海马片的电生理学研究表明，暴露于HIV/gp120tg的动物表现出强直后增强减少，而gp120表达和冰毒都导致长时程增强减少。定量逆转录-聚合酶链式反应阵列显示，gp120的表达、冰毒以及它们的组合都导致了GABA能和谷氨酸能神经传递系统特定成分的显著失调，为突触功能障碍和行为障碍提供了可能的机制。总之，HIV-1/gp120和冰毒都与神经病理和基因表达改变有关，导致了持久的行为损害。然而，联合接触冰毒和HIV-1/gp120的表达导致了最明显、持续时间最长的突触前和突触后改变，同时也损害了学习和记忆。
Methamphetamine (METH) abuse is frequent in individuals infected with human immunodeficiency virus type-1 (HIV-1) and is suspected to aggravate HIV-associated neurocognitive disorders (HAND). METH is a psychostimulant that compromises several neurotransmitter systems and HIV proteins trigger neuronal injury but the combined effects of viral infection and METH abuse are incompletely understood. In this study we treated transgenic mice expressing the HIV envelope protein gp120 in the brain (HIV/gp120tg) at 3–4 months of age with an escalating-dose, multiple-binge METH regimen. The long-term effects were analyzed after 6–7 months of drug abstinence employing behavioral tests and analysis of neuropathology, electrophysiology and gene expression. Behavioral testing showed that both HIV/gp120tg and WT animals treated with METH displayed impaired learning and memory. Neuropathological analysis revealed that METH similar to HIV/gp120 caused a significant loss of neuronal dendrites and pre-synaptic terminals in hippocampus and cerebral cortex of WT animals. Electrophysiological studies in hippocampal slices showed that METH exposed HIV/gp120tg animals displayed reduced post-tetanic potentiation, whereas both gp120 expression and METH lead to reduced long-term potentiation. A quantitative reverse transcription-polymerase chain reaction array showed that gp120 expression, METH and their combination each caused a significant dysregulation of specific components of GABAergic and glutamatergic neurotransmission systems, providing a possible mechanism for synaptic dysfunction and behavioral impairment. In conclusion, both HIV-1/gp120 and METH caused lasting behavioral impairment in association with neuropathology and altered gene expression. However, combined METH exposure and HIV-1/gp120 expression resulted in the most pronounced, long lasting pre-and post-synaptic alterations coinciding with impaired learning and memory.
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影响因子：
3.7
作者：
Cadet JL;McCoy MT;Cai NS;Krasnova IN;Ladenheim B;Beauvais G;Wilson N;Wood W;Becker KG;Hodges AB
通讯作者：
Hodges AB
影响因子：
1
作者：
Cisneros IE;Ghorpade A
通讯作者：
Ghorpade A
影响因子：
64.5
作者：
BEACH, ME;HAWKINS, RD;MAYFORD, M
通讯作者：
MAYFORD, M
影响因子：
3.7
作者：
Bourque, Melanie;Liu, Bin;Di Paolo, Therese
通讯作者：
Di Paolo, Therese
影响因子：
3.6
作者：
Abel, MS;Kohli, N
通讯作者：
Kohli, N