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Expression of Ephrin Receptors and Ligands in Postmortem Brains of HIV-Infected Subjects With and Without Cognitive Impairment | |
Yuferov, Vadim; Ho, Ann; Morgello, Susan; Yang, Yaning; Ott, Jurg; Kreek, Mary Jeanne; Yuferov, V (reprint author), Rockefeller Univ, 1230 York Ave, New York, NY 10021 USA. | |
心理所单位排序 | 4 |
摘要 | 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. |
关键词 | HIV dementia Human postmortem brain Ephrin receptors and ligands Chemokine receptors and ligands Neurocognitive impairment |
学科领域 | Cognitive Neuroscience |
2013 | |
语种 | 英语 |
发表期刊 | JOURNAL OF NEUROIMMUNE PHARMACOLOGY |
ISSN | 1674-2788 |
卷号 | 8期号:1页码:333-344 |
期刊论文类型 | 期刊论文 |
URL | 查看原文 |
收录类别 | SCI |
项目简介 | This work was supported by NIH NIDA-P60-05130 (MJK), NIMH-U01-MH083501 (SM). We thank Allie Sperry for help in performance of RT-PCR assays, and the patients and staff of the Manhattan HIV Brain Bank. We acknowledge the help of Dr. Keiichi Niikura, Adam J. Brownstein, and Molly Deutsch-Feldman for the art work of the diagram. |
WOS记录号 | WOS:000315441900031 |
资助机构 | NIH [NIDA-P60-05130, NIMH-U01-MH083501] |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://ir.psych.ac.cn/handle/311026/11512 |
专题 | 中国科学院心理健康重点实验室 |
通讯作者 | Yuferov, V (reprint author), Rockefeller Univ, 1230 York Ave, New York, NY 10021 USA. |
推荐引用方式 GB/T 7714 | Yuferov, Vadim,Ho, Ann,Morgello, Susan,et al. Expression of Ephrin Receptors and Ligands in Postmortem Brains of HIV-Infected Subjects With and Without Cognitive Impairment[J]. JOURNAL OF NEUROIMMUNE PHARMACOLOGY,2013,8(1):333-344. |
APA | Yuferov, Vadim.,Ho, Ann.,Morgello, Susan.,Yang, Yaning.,Ott, Jurg.,...&Yuferov, V .(2013).Expression of Ephrin Receptors and Ligands in Postmortem Brains of HIV-Infected Subjects With and Without Cognitive Impairment.JOURNAL OF NEUROIMMUNE PHARMACOLOGY,8(1),333-344. |
MLA | Yuferov, Vadim,et al."Expression of Ephrin Receptors and Ligands in Postmortem Brains of HIV-Infected Subjects With and Without Cognitive Impairment".JOURNAL OF NEUROIMMUNE PHARMACOLOGY 8.1(2013):333-344. |
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