title: Neuropsychological, Neurovirological and Neuroimmune Aspects of Abnormal GABAergic Transmission in HIV Infection.
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.
authors.affiliation: Department of Pathology, University of Texas Medical Branch, 301 University Blvd, 77555-0609, Galveston, TX, USA.|Department of Neuroscience and Cell Biology, University of Texas Medical Branch, 301 University Blvd, 77555-0609, Galveston, TX, USA.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Buzhdygan
authors.affiliation: Department of Pathology, University of Texas Medical Branch, 301 University Blvd, 77555-0609, Galveston, TX, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Lisinicchia
authors.affiliation: Department of Pathology, University of Texas Medical Branch, 301 University Blvd, 77555-0609, Galveston, TX, USA.
authors.forename: Vipulkumar
authors.initials: V
authors.lastname: Patel
authors.affiliation: Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Blvd, 77555-0609, Galveston, TX, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Johnson
authors.affiliation: Department of Pharmacology and Neuroscience, School of Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, 79430-6592, Lubbock, TX, USA.
authors.forename: Volker
authors.initials: V
authors.lastname: Neugebauer
authors.affiliation: Department of Pathology, University of Texas Medical Branch, 301 University Blvd, 77555-0609, Galveston, TX, USA.
authors.forename: Slobodan
authors.initials: S
authors.lastname: Paessler
authors.affiliation: Department of Preventive Medicine and Community Health, University of Texas Medical Branch, 301 University Blvd, 77555-0609, Galveston, TX, USA.
authors.forename: Kristofer
authors.initials: K
authors.lastname: Jennings
authors.affiliation: Department of Pathology, University of Texas Medical Branch, 301 University Blvd, 77555-0609, Galveston, TX, USA. bgelman@utmb.edu.|Department of Neuroscience and Cell Biology, University of Texas Medical Branch, 301 University Blvd, 77555-0609, Galveston, TX, USA. bgelman@utmb.edu.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gelman
mesh_terms: D015526:AIDS Dementia Complex / Q000276:immunology / Q000378:metabolism* / Q000523:psychology; D015331:Cohort Studies; D059330:GABAergic Neurons / Q000276:immunology / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism* / Q000523:psychology; D015497:HIV-1; D006801:Humans; D015213:Neuroimmunomodulation / Q000502:physiology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000276:immunology / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2
keywords: Autopsy; GABA; GABAergic; Glutamate decarboxylase; HIV associated neurocognitive disorders; HIV encephalitis
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