Expression of excitatory amino acid transporter-1 in brain macrophages and microglia of HIV-infected patients. A neuroprotective role for activated microglia?

Abstract

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.

• Authors: Anne Valérie Vallat-Decouvelaere, Fabrice Chrétien, Gabriel Gras, Gwenaelle Le Pavec, Dominique Dormont, Françoise Gray
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 62 Issue 5 Pg. 475-85 (May 2003) ISSN: 0022-3069 [Print] England
• PMID: 12769187 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Excitatory Amino Acid Transporter 1
• Glial Fibrillary Acidic Protein
• HLA-DR Antigens
• Neuroprotective Agents

Topics

• AIDS Dementia Complex (metabolism, pathology)
• Adult
• Aged
• Biomarkers
• Brain (cytology, metabolism, pathology)
• Excitatory Amino Acid Transporter 1 (metabolism)
• Glial Fibrillary Acidic Protein (metabolism)
• HIV Infections (metabolism, pathology)
• HLA-DR Antigens (metabolism)
• Humans
• Macrophages (metabolism)
• Male
• Microglia (metabolism)
• Middle Aged
• Neuroprotective Agents (metabolism)