Abnormal striatal dopaminergic synapses in National NeuroAIDS Tissue Consortium subjects with HIV encephalitis

Benjamin Gelman, Jeffrey A. Spencer, Charles E. Holzer, Vicki M. Soukup

Research output: Contribution to journalArticle

54 Citations (Scopus)

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 (D 2R) 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.

Original languageEnglish (US)
Pages (from-to)410-420
Number of pages11
JournalJournal of NeuroImmune Pharmacology
Volume1
Issue number4
DOIs
StatePublished - Dec 2006

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Corpus Striatum
Encephalitis
Synapses
HIV
Tyrosine 3-Monooxygenase
Synaptic Transmission
Protein Isoforms
Acquired Immunodeficiency Syndrome
Dopamine Plasma Membrane Transport Proteins
Proteins
Dopamine Receptors
Street Drugs
Virus Diseases
Risk-Taking
Psychotic Disorders
Substance-Related Disorders
Dementia
Autopsy
Messenger RNA
Brain

Keywords

  • Addiction
  • Autopsy
  • Dementia
  • Dopamine
  • Dopamine receptor
  • Dopamine reuptake
  • Dopamine transporter
  • Dopaminergic
  • HIV encephalitis
  • National neuroAIDS
  • Synaptic transmission
  • Tissue consortium
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Pharmacology
  • Immunology and Allergy
  • Immunology
  • Neuroscience (miscellaneous)

Cite this

Abnormal striatal dopaminergic synapses in National NeuroAIDS Tissue Consortium subjects with HIV encephalitis. / Gelman, Benjamin; Spencer, Jeffrey A.; Holzer, Charles E.; Soukup, Vicki M.

In: Journal of NeuroImmune Pharmacology, Vol. 1, No. 4, 12.2006, p. 410-420.

Research output: Contribution to journalArticle

Gelman, Benjamin ; Spencer, Jeffrey A. ; Holzer, Charles E. ; Soukup, Vicki M. / Abnormal striatal dopaminergic synapses in National NeuroAIDS Tissue Consortium subjects with HIV encephalitis. In: Journal of NeuroImmune Pharmacology. 2006 ; Vol. 1, No. 4. pp. 410-420.
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