Expression of excitatory amino acid transporter-1 (EAAT-1) in brain macrophages and microglia of patients with prion diseases

Fabrice Chrétien, Gwenaelle Le Pavec, Anne Valérie Vallat-Decouvelaere, Marie Bernadette Delisle, Emmanuelle Uro-Coste, James W. Ironside, Pierluigi Gambetti, Piero Parchi, Christophe Créminon, Dominique Dormont, Jacqueline Mikol, Françoise Gray, Gabriel Gras

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The mechanisms of neuronal apoptosis in prion diseases are unclear. Experimental studies suggest that it may result from 2 associated mechanisms: glutamate-mediated excitotoxicity and oxidative stress. Recent studies showed that activated macrophages/microglia (AMM) express excitatory amino acid transporters (EAATs) in HIV infection, suggesting that they may play a neuroprotective role by clearing extra-cellular glutamate and producing anti-oxidant glutathione. In order to test this hypothesis in prion diseases, samples from cerebral cortex, striatum, thalamus, and cerebellum from 14 patients with Creutzfeldt-Jakob disease (8 sporadic, 2 familial, 2 iatrogenic, and 2 variant), and 4 with fatal familial insomnia (3 homozygous Met/Met at codon 129 of the PRNP gene, 1 heterozygous Met/Val), and 3 controls were immunostained for EAAT-1, GFAP, HLA-DR, CD68, IL-1, caspase 3, and PrP. In prion diseases, EAAT-1 immunopositivity was found in affected areas. Only AMM, interstitial, perivascular, perineuronal (sometimes around apoptotic neurons), or close to reactive astrocytes, expressed EAAT-1. Astrocyte EAAT-1 expression was scarcely detectable in controls and was not detected in prion disease cases. The proportion of AMM expressing EAAT-1 did not correlate with the severity of neuronal apoptosis, spongiosis, astrocytosis, microgliosis, or PrP deposition, but only with disease duration. Occasional EAAT-1 expressing AMM were found in patients with short survival, whereas diffuse EAAT-1 expression by AMM was observed in cases with long survival (24 to 33 months) that most often were heterozygous for Met/Val at codon 129 of the PRNP gene. Our findings suggest that AMM may develop a partial neuroprotective function in long-lasting prion diseases, although it does not seem to efficiently prevent neurological and neuropathological deterioration. Whether this neuroprotective function of microglia is the cause or the effect of longer survival needs to be clarified.

Original languageEnglish
Pages (from-to)1058-1071
Number of pages14
JournalJournal of Neuropathology and Experimental Neurology
Volume63
Issue number10
Publication statusPublished - Oct 2004

Fingerprint

Excitatory Amino Acid Transporter 1
Prion Diseases
Microglia
Macrophages
Brain
Codon
Astrocytes
Survival
Glutamic Acid
Fatal Familial Insomnia
Apoptosis
Amino Acid Transport Systems
Excitatory Amino Acids
Gliosis
HLA-DR Antigens
Thalamus
Interleukin-1
Oxidants
Caspase 3
Cerebral Cortex

Keywords

  • Creutzfeldt-Jakob disease
  • Excitatory amino acid transporter (EAAT)
  • Fatal familial insomnia
  • Glutamate
  • Macrophage
  • Microglia
  • Prion diseases

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Chrétien, F., Le Pavec, G., Vallat-Decouvelaere, A. V., Delisle, M. B., Uro-Coste, E., Ironside, J. W., ... Gras, G. (2004). Expression of excitatory amino acid transporter-1 (EAAT-1) in brain macrophages and microglia of patients with prion diseases. Journal of Neuropathology and Experimental Neurology, 63(10), 1058-1071.

Expression of excitatory amino acid transporter-1 (EAAT-1) in brain macrophages and microglia of patients with prion diseases. / Chrétien, Fabrice; Le Pavec, Gwenaelle; Vallat-Decouvelaere, Anne Valérie; Delisle, Marie Bernadette; Uro-Coste, Emmanuelle; Ironside, James W.; Gambetti, Pierluigi; Parchi, Piero; Créminon, Christophe; Dormont, Dominique; Mikol, Jacqueline; Gray, Françoise; Gras, Gabriel.

In: Journal of Neuropathology and Experimental Neurology, Vol. 63, No. 10, 10.2004, p. 1058-1071.

Research output: Contribution to journalArticle

Chrétien, F, Le Pavec, G, Vallat-Decouvelaere, AV, Delisle, MB, Uro-Coste, E, Ironside, JW, Gambetti, P, Parchi, P, Créminon, C, Dormont, D, Mikol, J, Gray, F & Gras, G 2004, 'Expression of excitatory amino acid transporter-1 (EAAT-1) in brain macrophages and microglia of patients with prion diseases', Journal of Neuropathology and Experimental Neurology, vol. 63, no. 10, pp. 1058-1071.
Chrétien F, Le Pavec G, Vallat-Decouvelaere AV, Delisle MB, Uro-Coste E, Ironside JW et al. Expression of excitatory amino acid transporter-1 (EAAT-1) in brain macrophages and microglia of patients with prion diseases. Journal of Neuropathology and Experimental Neurology. 2004 Oct;63(10):1058-1071.
Chrétien, Fabrice ; Le Pavec, Gwenaelle ; Vallat-Decouvelaere, Anne Valérie ; Delisle, Marie Bernadette ; Uro-Coste, Emmanuelle ; Ironside, James W. ; Gambetti, Pierluigi ; Parchi, Piero ; Créminon, Christophe ; Dormont, Dominique ; Mikol, Jacqueline ; Gray, Françoise ; Gras, Gabriel. / Expression of excitatory amino acid transporter-1 (EAAT-1) in brain macrophages and microglia of patients with prion diseases. In: Journal of Neuropathology and Experimental Neurology. 2004 ; Vol. 63, No. 10. pp. 1058-1071.
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AU - Ironside, James W.

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