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Striatal glutamate induces retrograde excitotoxicity and neuronal degeneration of intralaminar thalamic nuclei: their potential relevance for P arkinson's disease
Author(s) -
Morales Ingrid,
Sabate Magdalena,
Rodriguez Manuel
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12205
Subject(s) - substantia nigra , excitotoxicity , striatum , dopaminergic , neuroscience , glutamate receptor , dopamine , denervation , nigrostriatal pathway , chemistry , biology , endocrinology , biochemistry , receptor
An over‐stimulation of nigral glutamate ( GLU ) receptors has been proposed as a cause of the progression of the dopamine ( DA ) cell degeneration (excitotoxicity) which characterizes P arkinson's disease. The possible toxic action of striatal GLU (retrograde excitotoxicity) on these cells, and on other neurons which innervate the striatum and which also degenerate in P arkinson's disease (thalamostriatal cells of the intralaminar thalamic nuclei), is still practically unexplored. The retrograde excitotoxicity of striatal GLU on DA ergic mesostriatal and GLU ergic thalamostriatal cells was tested here by studying these cells 6 weeks after striatal perfusion of GLU by reverse microdialysis. GLU perfusion induced the striatal denervation of thalamic inputs (as revealed by vesicular glutamate transporter 2) and the remote degeneration of intralaminar neurons. In both centres, these effects were accompanied by microglial activation. Similar responses were not observed for nigrostriatal neurons, which showed no dopaminergic striatal denervation, no microglial activation in the substantia nigra and no changes in the number of dopaminergic cells in the substantia nigra. The inhibition of DA ergic transmission increased the extrasynaptic GLU levels in the striatum (evaluated by microdialysis), an effect observed after the local administration of agonists and antagonists of DA ergic transmission, and after the peripheral administration of levodopa (which increased the DA and decreased the GLU levels in the striatum of rats with an experimental DA ergic denervation of this centre). The data presented show that striatal GLU induced a retrograde excitotoxicity which did not affect all striatal inputs in the same way and which could be involved in the cell degeneration of the intralaminar nuclei of the thalamus generally observed in P arkinson's disease.