HIV-1, methamphetamine and astrocyte glutamate regulation: combined excitotoxic implications for neuro-AIDS.
HIV-1, methamphetamine and astrocyte glutamate regulation: combined excitotoxic implications for neuro-AIDS.
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DOI：
10.2174/157016212802138832
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发表时间：
2012-07
影响因子：
1
通讯作者：
Ghorpade A
中科院分区：
文献类型：
--
作者：
Cisneros IE;Ghorpade A
谷氨酸是大脑中最丰富的兴奋性递质，如果调节不当，可导致神经毒性。兴奋性毒性是突触中谷氨酸浓度异常调节的直接结果，并且是与神经退行性疾病相关的常见神经毒性介质。众所周知，甲基苯丙胺（METH），一种具有高滥用潜力的强效中枢神经兴奋剂，和人类免疫缺陷病毒（HIV）-1与神经认知功能障碍的进展有关。两者都已被证明会诱导常见的神经退行性作用，如星形胶质细胞增生、血脑屏障完整性受损和大脑兴奋性毒性。减少从神经元突触的谷氨酸摄取可能导致谷氨酸在细胞外空间中的积累。星形胶质细胞表达谷氨酸转运蛋白，负责突触的大部分谷氨酸摄取以及囊泡谷氨酸释放。然而，在METH和HIV-1的背景下星形胶质细胞介导的兴奋性毒性的细胞和分子机制尚不明确。综述的主题包括谷氨酸转运蛋白的失调，特别是兴奋性氨基酸转运蛋白2，代谢型谷氨酸受体的表达和囊泡胞吐释放谷氨酸。我们还讨论了谷氨酸浓度失调通过星形胶质细胞的谷氨酸合成和代谢酶的表达。最后，我们讨论了最近的证据表明，各种星形胶质细胞和神经元的串扰机制牵连谷氨酸调节。星形胶质细胞在与METH/HIV-1诱导的兴奋性毒性相关的神经病理学中发挥重要作用。我们希望阐明药物滥用和HIV-1感染期间星形胶质细胞在谷氨酸调节中的共同细胞和分子途径。
Glutamate, the most abundant excitatory transmitter in the brain can lead to neurotoxicity when not properly regulated. Excitotoxicity is a direct result of abnormal regulation of glutamate concentrations in the synapse, and is a common neurotoxic mediator associated with neurodegenerative disorders. It is well accepted that methamphetamine (METH), a potent central nervous stimulant with high abuse potential, and human immunodeficiency virus (HIV)-1 are implicated in the progression of neurocognitive malfunction. Both have been shown to induce common neurodegenerative effects such as astrogliosis, compromised blood brain barrier integrity, and excitotoxicity in the brain. Reduced glutamate uptake from neuronal synapses likely leads to the accumulation of glutamate in the extracellular spaces. Astrocytes express the glutamate transporters responsible for majority of the glutamate uptake from the synapse, as well as for vesicular glutamate release. However, the cellular and molecular mechanisms of astrocyte-mediated excitotoxicity in the context of METH and HIV-1 are undefined. Topics reviewed include dysregulation of the glutamate transporters, specifically excitatory amino acid transporter-2, metabotropic glutamate receptor(s) expression and the release of glutamate by vesicular exocytosis. We also discuss glutamate concentration dysregulation through astrocytic expression of enzymes for glutamate synthesis and metabolism. Lastly, we discuss recent evidence of various astrocyte and neuron crosstalk mechanisms implicated in glutamate regulation. Astrocytes play an essential role in the neuropathologies associated with METH/HIV-1-induced excitotoxicity. We hope to shed light on common cellular and molecular pathways astrocytes share in glutamate regulation during drug abuse and HIV-1 infection.
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影响因子：
3.2
作者：
Conant, K;St Hillaire, C;Nath, A
通讯作者：
Nath, A
DOI：
10.1523/jneurosci.1064-09.2009
发表时间：
2009-10-14
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Abdul HM;Sama MA;Furman JL;Mathis DM;Beckett TL;Weidner AM;Patel ES;Baig I;Murphy MP;LeVine H 3rd;Kraner SD;Norris CM
通讯作者：
Norris CM
影响因子：
6.2
作者：
Benediktsson, Adrienne M.;Marrs, Glen S.;Tu, Jian Cheng;Worley, Paul F.;Roth-Stein, Jeffrey D.;Bergles, Dwight E.;Dailey, Michael E.
通讯作者：
Dailey, Michael E.
DOI：
10.4049/jimmunol.1002235
发表时间：
2011-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bethel-Brown C;Yao H;Callen S;Lee YH;Dash PK;Kumar A;Buch S
通讯作者：
Buch S
影响因子：
4.7
作者：
Biber, K;Laurie, DJ;Boddeke, HWGM
通讯作者：
Boddeke, HWGM