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Abnormal Striatal Dopaminergic Synapses in National NeuroAIDS Tissue Consortium Subjects with HIV Encephalitis

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Abstract

People with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) have neurological problems that overlap with diseases associated with abnormal dopaminergic (DAergic) synaptic transmission, including subcortical dementia, motor slowing, psychosis, and drug addiction. Previous study has suggested that DAergic tone may be decreased in HIV/AIDS, but biochemical confirmation of that tenet is still lacking. To that end, this study addresses the neurochemical interaction between HIV infection and DAergic synaptic transmission in human brain specimens. Protein markers of DAergic synapses were characterized in homogenates of the corpus striatum from individuals with HIV encephalitis (HIVE) and seronegative controls from the autopsy cohort of the National NeuroAIDS Tissue Consortium. Striatal DAergic markers were abnormal in HIVE. Abnormal presynaptic markers included decreased tyrosine hydroxylase (TH) protein and decreased phosphorylated TH. The presynaptic dopamine reuptake transporter (DAT) was increased reciprocally. Postsynaptic abnormalities included decreased dopamine receptor type 2 (D2R) and increased D3R. There was preferential loss of the alternatively spliced long isoform of D2R relative to the short isoform. Abnormal DAergic synapse proteins were significantly correlated with the HIV Gag mRNA transcripts amplified in striatal extracts. These synaptic changes resemble shifts that occur when DAergic tone is increased experimentally. Increased DAergic tone leads to heightened salience for drugs of abuse, increases behaviors that increase the risk of HIV transmission, and might decrease compliance with antiretroviral medication regimens.

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Acknowledgements

We thank Joshua G. Lisinicchia and Alyson R. Clayborn for technical assistance, and Jean Richey, RN, and the excellent nursing program staff of the Texas NeuroAIDS Research Center. Mr. Steve Schuenke assisted with illustration. This research was supported by the National Institutes of Health, R24 NS45491 and R01 MH69200.

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Authors and Affiliations

  1. Department of Pathology, Route 0785, University of Texas Medical Branch, Galveston, Texas, 77555-0785, USA

    Benjamin B. Gelman & Jeffrey A. Spencer

  2. Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX, 77555-0785, USA

    Benjamin B. Gelman

  3. Department of Psychiatry, University of Texas Medical Branch, Galveston, TX, 77555-0189, USA

    Charles E. Holzer III

  4. Department of Neurology, University of Texas Medical Branch, Galveston, TX, 77555-0539, USA

    Vicki M. Soukup

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  1. Benjamin B. Gelman
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  2. Jeffrey A. Spencer
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  4. Vicki M. Soukup
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Correspondence to Benjamin B. Gelman.

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This paper was presented at the 12th Annual Society for Neuroimmune Pharmacology Conference on April 6, 2006 in Santa Fe, NM, USA.

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Gelman, B.B., Spencer, J.A., Holzer, C.E. et al. Abnormal Striatal Dopaminergic Synapses in National NeuroAIDS Tissue Consortium Subjects with HIV Encephalitis. Jrnl Neuroimmune Pharm 1, 410–420 (2006). https://doi.org/10.1007/s11481-006-9030-6

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