title: Reduced expression of excitatory amino acid transporter 2 and diffuse microglial activation in the cerebral cortex in AIDS cases with or without HIV encephalitis.
abstract: To determine the relationship between the human immunodeficiency virus type 1 (HIV-1) encephalitis (HIVE) and diffuse poliodystrophy in the acquired immunodeficiency syndrome dementia complex, we examined the neuropathologic features in brain autopsy tissue specimens of HIV-1-infected patients with (n = 11) or without HIVE (n = 9). The brains were free of opportunistic diseases and major cerebrovascular lesions. In both groups, there was diffuse microglial activation, astrocytic gliosis, and decreased excitatory amino acid transporter 2 (EAAT-2) immunoreactivity. These changes did not correlate either with the severity of encephalitis or local HIV-1 infection as detected by p24 immunostaining. Some activated microglia expressed EAAT-2; interleukin-1beta and tumor necrosis factor were detected only in microglial nodules of HIVE cases but not in areas with diffusely activated microglia. There was a significant negative correlation between the areas of EAAT-2 expression and numbers of activated microglia (p < 0.01) in cases with decreased EAAT-2. These data indicate that diffuse cortical changes may occur independently of HIVE in acquired immunodeficiency syndrome patients. The expression of EAAT-2 by activated microglia suggests that they might exert a compensatory effect that protects neurons from glutamate neurotoxicity.
authors.affiliation: Division of Molecular Pathology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima, Japan.
authors.forename: Hui Qin
authors.initials: HQ
authors.lastname: Xing
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hayakawa
authors.forename: Ellen
authors.initials: E
authors.lastname: Gelpi
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kubota
authors.forename: Herbert
authors.initials: H
authors.lastname: Budka
authors.forename: Shuji
authors.initials: S
authors.lastname: Izumo
mesh_terms: D015526:AIDS Dementia Complex / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D019610:Cytoprotection / Q000276:immunology; D015536:Down-Regulation / Q000502:physiology; D027342:Excitatory Amino Acid Transporter 2; D005911:Gliosis / Q000378:metabolism / Q000473:pathology*; D050491:Glutamate Plasma Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000032:analysis / Q000378:metabolism; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
chemical_list: D015415:Biomarkers; D027342:Excitatory Amino Acid Transporter 2; D050491:Glutamate Plasma Membrane Transport Proteins; D016655:HIV Core Protein p24; D053583:Interleukin-1beta; C493397:SLC1A2 protein, human; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid