Self-induced accumulation of glutamate in striatal astrocytes and basal ganglia excitotoxicity.
Excitotoxicity induced by high levels of extracellular glutamate (GLU) has been proposed as a cause of cell degeneration in basal ganglia disorders. This phenomenon is normally prevented by the astrocytic GLU-uptake and the GLU-catabolization to less dangerous molecules. However, high-GLU can induce reactive gliosis which could change the neuroprotective role of astrocytes. The striatal astrocyte response to high GLU was studied here in an in vivo rat preparation. The transient striatal perfusion of GLU (1 h) by reverse microdialysis induced complex reactive gliosis which persisted for weeks and which was different for radial-like glia, protoplasmic astrocytes and fibrous astrocytes. This gliosis was accompanied by a persistent cytosolic accumulation of GLU (immunofluorescence quantified by confocal microscope), which persisted for weeks (self-induced glutamate accumulation), and which was associated to a selective decrease of glutamine synthetase activity. This massive and persistent self-induced glutamate accumulation in striatal astrocytes could be an additional factor for the GLU-induced excitotoxicity, which has been implicated in the progression of different basal ganglia disorders.
Laboratory of Neurobiology and Experimental Neurology, Department of Physiology, Faculty of Medicine, University of La Laguna, La Laguna, Tenerife, Canary Islands, Spain.
Ingrid
I
Morales
Manuel
M
Rodriguez
D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D003342:Corpus Striatum / Q000473:pathology*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D017551:Microdialysis / Q000379:methods; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005904:Glial Fibrillary Acidic Protein; D005974:Glutamate-Ammonia Ligase; D018698:Glutamic Acid; C067980:CD68 antigen, human; D000097382:CD68 Molecule