Expression of ephrin receptors and ligands in postmortem brains of HIV-infected subjects with and without cognitive impairment.
Expression of ephrin receptors and ligands in postmortem brains of HIV-infected subjects with and without cognitive impairment.
复制标题
有或没有认知障碍的 HIV 感染者死后大脑中肝配蛋白受体和配体的表达
DOI：
10.1007/s11481-012-9429-1
复制
发表时间：
2013-03
影响因子：
6.2
通讯作者：
Kreek, Mary Jeanne
中科院分区：
文献类型：
--
作者：
Yuferov, Vadim;Ho, Ann;Morgello, Susan;Yang, Yaning;Ott, Jurg;Kreek, Mary Jeanne
关键词：
尽管联合抗逆转录病毒疗法取得了成功，但许多感染者仍存在艾滋病毒相关的神经认知障碍。早期研究表明，神经认知障碍与谷氨酸毒性和突触树突损伤有关。我们研究了四个肝配蛋白基因表达的变化，参与突触形成和招募谷氨酸受体的突触，在尾状核和前扣带回在死后的认知特征的HIV感染的受试者的大脑，沿着与神经元和星形胶质细胞/大胶质细胞标记物的表达。从曼哈顿HIV脑库获得HIV感染者和对照受试者的死后组织。HIV感染受试者在死亡前接受神经认知评估。使用SYBR绿色RT-PCR进行趋化因子受体和趋化因子（CCR 5、CXCR 4、CCL 2）、星形胶质细胞/小胶质细胞标志物（GFAP、CD 163、CD 68）、神经元标志物SNAP 25、肝配蛋白受体EPHA 4和EPHB 2以及肝配蛋白配体EFNB 1和EFNB 2的基因的mRNA定量。促炎趋化因子和神经胶质细胞/巨噬细胞mRNA水平在这两个地区显着高于HIV+比HIV-的主题。HIV阳性组尾状核EPHA 4和EFNB 2 mRNA水平及前扣带回EPHB 2 mRNA水平显著低于对照组（p<0.002，p <0.02，p < 0.05）。这些转录本还显示出与HIV感染组内的免疫状态和认知功能的相关性。尾状核EFNB 2 mRNA表达水平的降低与CD 4计数的降低相关（P< 0.05）。认知关联仅限于扣带，其中EPHB 2 mRNA水平降低与更好的整体认知状态相关。扣带回EPHB 2表达的减少可能代表了一种代偿机制，在慢性炎症面前使兴奋性毒性损伤最小化。
Despite the successes of combination antiretroviral therapy, HIV-associated neurocognitive disorders persist in many infected individuals. Earlier studies showed that neurocognitive impairment was associated with glutamate toxicity and synaptodendritic damage. We examined alterations in expression of four ephrin genes that are involved in synapse formation and recruitment of glutamate receptors to synapses, in the caudate and anterior cingulate in postmortem brain of cognitively characterized HIV-infected subjects, along with expression of neuronal and astroglial/macroglial markers. Postmortem tissues of HIV-infected and control subjects were obtained from the Manhattan HIV Brain Bank. HIV-infected subjects underwent neurocognitive assessment prior to death. Quantification of mRNA of genes of chemokine receptors and chemokines (CCR5, CXCR4, CCL2), astroglial/microglial markers (GFAP, CD163, CD68), the neuronal marker SNAP25, ephrin receptors EPHA4 and EPHB2, and ephrin ligands EFNB1 and EFNB2 was performed using SYBR Green RT-PCR. Proinflammatory chemokine and glial/macrophage mRNA levels in both regions were significantly greater in HIV+ than in HIV- subjects. Levels of EPHA4 and EFNB2 mRNA in the caudate, and EPHB2 mRNA in anterior cingulate were significantly lower in HIV+ subjects (p< 0.002,p< 0.02,p< 0.05, respectively). These transcripts also showed correlations with immune status and cognitive function within the HIV-infected group. Decreased levels of EFNB2 mRNA in the caudate correlated with lower CD4 counts (P< 0.05). Cognitive associations were limited to the cingulate, where decreased levels of EPHB2 mRNA were associated with better global cognitive status. Decreased cingulate expression of EPHB2 may represent a compensatory mechanism minimizing excitotoxic injury in the face of chronic inflammation.
登录
查看更多内容
影响因子：
7
作者：
Lee, HK;Hsu, AK;Pavlidis, P
通讯作者：
Pavlidis, P
影响因子：
3.2
作者：
Heaton, Robert K.;Franklin, Donald R.;Ellis, Ronald J.;McCutchan, J. Allen;Letendre, Scott L.;LeBlanc, Shannon;Corkran, Stephanie H.;Duarte, Nichole A.;Clifford, David B.;Woods, Steven P.;Collier, Ann C.;Marra, Christina M.;Morgello, Susan;Mindt, Monica Rivera;Taylor, Michael J.;Marcotte, Thomas D.;Atkinson, J. Hampton;Wolfson, Tanya;Gelman, Benjamin B.;McArthur, Justin C.;Simpson, David M.;Abramson, Ian;Gamst, Anthony;Fennema-Notestine, Christine;Jernigan, Terry L.;Wong, Joseph;Grant, Igor
通讯作者：
Grant, Igor
影响因子：
4.7
作者：
Bouvier, David;Corera, Amadou T.;Doucet, Guy
通讯作者：
Doucet, Guy
影响因子：
25
作者：
Grunwald, IC;Korte, M;Klein, R
通讯作者：
Klein, R
影响因子：
9.9
作者：
Ferrarese, C;Aliprandi, A;Frattola, L
通讯作者：
Frattola, L