Up-regulation of glutamate concentration in the putamen and in the prefrontal cortex of asymptomatic SIVmac251-infected macaques without major brain involvement.
We quantified putamen and prefrontal cortex metabolites in macaques with simian immunodeficiency virus infection and searched for virological and histological correlates. Fourteen asymptomatic macaques infected since 8-78 months (median: 38) were compared with eight uninfected ones. Absolute concentrations of acetate, alanine, aspartate, choline, creatine, GABA, glutamate, glutamine, lactate, myo-inositol, N-acetylaspartate, taurine and valine were determined by ex vivo proton magnetic resonance spectroscopy. Glutamate concentration in the CSF was determined by HPLC. Gliosis was assessed by glial fibrillary acidic protein and CD68 immunohistochemistry. Glutamate concentration was slightly increased in the prefrontal cortex (19%, p = 0.0152, t-test) and putamen (13%, p = 0.0354, t-test) of the infected macaques, and was unaffected in the CSF. Myo-inositol concentration was increased in the prefrontal cortex only (27%, p = 0.0136). The concentrations of glutamate and myo-inositol in the prefrontal cortex were higher in the animals with marked or intense microgliosis (p = 0.0114). The other studied metabolites, including N-acetylaspartate, were not altered. Glutamate concentration may thus increase in the cerebral parenchyma in asymptomatic animals, but is not accompanied by a detectable decrease in N-acetylaspartate concentration (neuronal dysfunction). Thus, there are probably compensatory mechanisms that may limit glutamate increase and/or counterbalance its effects.
Bossuet
Christophe
C
Service de Neurovirologie, UMR-E1 CEA, Université Paris-Sud, Centre de Recherches du Service de Santé des Armées, Ecole Pratique des Hautes Etudes, Institut Paris-Sud Cytokines, Fontenay-aux-Roses, France.
Vaufrey
Françoise
F
Condé
Françoise
F
Chrétien
Fabrice
F
Pichon
Jacques
J
Hantraye
Philippe
P
Le Grand
Roger
R
Dormont
Dominique
D
Gras
Gabriel
G
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001923:Brain Chemistry; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D020805:Central Nervous System Viral Diseases / Q000175:diagnosis; D002851:Chromatography, High Pressure Liquid; D005434:Flow Cytometry / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D010949:Plasma / Q000821:virology; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000821:virology; D011506:Proteins / Q000378:metabolism; D011699:Putamen / Q000378:metabolism* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013997:Time Factors; D019562:Viral Load / Q000379:methods; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005904:Glial Fibrillary Acidic Protein; D018698:Glutamic Acid; D011506:Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule