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Expression of Ephrin Receptors and Ligands in Postmortem Brains of HIV-Infected Subjects With and Without Cognitive Impairment

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Abstract

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.

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Acknowledgments

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.

Conflict of interests

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, 10065, USA

    Vadim Yuferov, Ann Ho & Mary Jeanne Kreek

  2. Department of Neurology, Neuroscience and Pathology, Mount Sinai Medical Center, New York, NY, 10029, USA

    Susan Morgello

  3. University of Science and Technology, Hefei, Anhui Province, China

    Yaning Yang

  4. Institute of Psychology CAS, Beijing, China

    Jurg Ott

  5. The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA

    Vadim Yuferov

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  1. Vadim Yuferov
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  2. Ann Ho
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  5. Jurg Ott
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  6. Mary Jeanne Kreek
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Correspondence to Vadim Yuferov.

Additional information

This work was supported by NIH NIDA-P60-05130 (MJK), NIMH-U01-MH083501 (SM), NSFC-10971210 (YY) (China Natural Science Foundation)

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Yuferov, V., Ho, A., Morgello, S. et al. Expression of Ephrin Receptors and Ligands in Postmortem Brains of HIV-Infected Subjects With and Without Cognitive Impairment. J Neuroimmune Pharmacol 8, 333–344 (2013). https://doi.org/10.1007/s11481-012-9429-1

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  • DOI: https://doi.org/10.1007/s11481-012-9429-1

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