Expression of excitatory amino acid transporter-1 in brain macrophages and microglia of HIV-infected patients. A neuroprotective role for activated microglia?
Recent experimental studies showed that activated macrophages/microglia (AMM) express excitatory amino acid transporters (EAATs), suggesting that, in addition to their neurotoxic properties, they also have a neuroprotective role by clearing extracellular glutamate and producing antioxidant glutathione. To test this hypothesis in human, the brain of 12 HIV-positive patients and 3 controls were immunostained for EAAT-1. EAAT-1 was expressed by AMM in all HIV-infected cases but not in HIV-negative controls. Expression varied according to the disease stage. In 5 cases with active HIV-encephalitis (HIVE), AMM strongly expressed EAAT-1 in the white matter and basal ganglia, analogous to HLA-DR and CD68 expression. There was weaker expression in the cortex and perineuronal microglial cells were not involved. In a case with "burnt out" HIVE following highly active antiretroviral therapy (HAART), EAAT-1 expression was mild, identical to that of HLA-DR and CD68 in the white matter and cortex and involved perineuronal microglial cells. In 3 AIDS patients without HIVE and in 3 pre-AIDS cases, EAAT-1 expression in the white matter was weaker than HLA-DR and CD68 expression; there was stronger correlation in the gray matter where perineuronal microglial cells were stained predominantly. Our findings in humans tend to confirm that AMM, particularly perineuronal microglial cells, play a neuroprotective role in the early stages of HIV infection and, possibly, following treatment. This is in keeping with the early microglial activation seen in pre-AIDS cases, and the late occurrence of neuronal loss. It may also explain the reversible cognitive disorders following treatment in some cases.
Vallat-Decouvelaere
Anne Valérie
AV
Service d'Anatomie et Cytologie Pathologiques, Hôpital Calmette, Lille, France.
Chrétien
Fabrice
F
Gras
Gabriel
G
Le Pavec
Gwenaelle
G
Dormont
Dominique
D
Gray
Françoise
F
D015526:AIDS Dementia Complex / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D015415:Biomarkers; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism* / Q000473:pathology; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000378:metabolism*; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000378:metabolism*
D015415:Biomarkers; D027341:Excitatory Amino Acid Transporter 1; D005904:Glial Fibrillary Acidic Protein; D006684:HLA-DR Antigens; D018696:Neuroprotective Agents