Neuropsychological, Neurovirological and Neuroimmune Aspects of Abnormal GABAergic Transmission in HIV Infection.

TitleNeuropsychological, Neurovirological and Neuroimmune Aspects of Abnormal GABAergic Transmission in HIV Infection.
Publication TypeJournal Article
Year of Publication2016
AuthorsBuzhdygan, T, Lisinicchia, JG, Patel, V, Johnson, K, Neugebauer, V, Paessler, S, Jennings, K, Gelman, B
JournalJ Neuroimmune Pharmacol
Volume11
Issue2
Pagination279-93
Date Published2016 Jun
ISSN1557-1904
KeywordsAIDS Dementia Complex, Cohort Studies, GABAergic Neurons, Glutamate Decarboxylase, HIV Infections, HIV-1, Humans, Internal, Neuroimmunomodulation, Neuropsychological Tests, Prefrontal Cortex, Synaptic Transmission
Abstract

The prevalence of HIV-associated neurocognitive disorders (HAND) remains high in patients with effective suppression of virus replication by combination antiretroviral therapy (cART). Several neurotransmitter systems were reported to be abnormal in HIV-infected patients, including the inhibitory GABAergic system, which mediates fine-tuning of neuronal processing and plays an essential role in cognitive functioning. To elucidate the role of abnormal GABAergic transmission in HAND, the expression of GABAergic markers was measured in 449 human brain specimens from HIV-infected patients with and without HAND. Using real-time polymerase chain reaction, immunoblotting and immunohistochemistry we found that the GABAergic markers were significantly decreased in most sectors of cerebral neocortex, the neostriatum, and the cerebellum of HIV-infected subjects. Low GABAergic expression in frontal neocortex was correlated significantly with high expression of endothelial cell markers, dopamine receptor type 2 (DRD2L), and preproenkephalin (PENK) mRNAs, and with worse performance on tasks of verbal fluency. Significant associations were not found between low GABAergic mRNAs and HIV-1 RNA concentration in the brain, the history of cART, or HIV encephalitis. Pathological evidence of neurodegeneration of the affected GABAergic neurons was not present. We conclude that abnormally low expression of GABAergic markers is prevalent in HIV-1 infected patients. Interrelationships with other neurotransmitter systems including dopaminergic transmission and with endothelial cell markers lend added support to suggestions that synaptic plasticity and cerebrovascular anomalies are involved with HAND in virally suppressed patients.

DOI10.1007/s11481-016-9652-2
Alternate JournalJ Neuroimmune Pharmacol
PubMed ID26829944
PubMed Central IDPMC4848342
Grant ListU24 MH100929 / MH / NIMH NIH HHS / United States
U24 MH100925 / MH / NIMH NIH HHS / United States
U24 MH100931 / MH / NIMH NIH HHS / United States
U24 MH100928 / MH / NIMH NIH HHS / United States
R01 NS072005 / NS / NINDS NIH HHS / United States
R01 NS081121 / NS / NINDS NIH HHS / United States
R01 MH101017 / MH / NIMH NIH HHS / United States
R01 MH079886 / MH / NIMH NIH HHS / United States
U24 MH100930 / MH / NIMH NIH HHS / United States
R01 NS038261 / NS / NINDS NIH HHS / United States