Reduced expression of excitatory amino acid transporter 2 and diffuse microglial activation in the cerebral cortex in AIDS cases with or without HIV encephalitis.
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.
Xing
Hui Qin
HQ
Division of Molecular Pathology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima, Japan.
Hayakawa
Hitoshi
H
Gelpi
Ellen
E
Kubota
Ryuji
R
Budka
Herbert
H
Izumo
Shuji
S
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
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