RT info:eu-repo/semantics/article
T1 Striatal glutamate induces retrograde excitotoxicity and neuronal degeneration of intralaminar thalamic nuclei: their potential relevance for Parkinson's disease
A1 Morales Pérez, Ingrid
A1 Sabaté, Magdalena
A1 Rodríguez, Manuel
A2 Ciencias Médicas Básicas
A2 Grupo de Neurobiología y Neurología Experimental
K1 glutamate
K1 intralaminar thalamic nuclei
K1 Parkinson’s disease
K1 retrograde excitotoxicity
K1 striatum
K1 substantia nigra
AB 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 Parkinson’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 Parkinson’s disease (thalamostriatal cells of the intralaminar thalamic nuclei), is still practically unexplored. The retrograde excitotoxicity of striatal GLU on DAergic mesostriatal and GLUergic 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 DAergic transmission increased the extrasynaptic GLU levels in the striatum (evaluated by microdialysis), an effect observed after the local administration of agonists and antagonists of DAergic 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 DAergic 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 Parkinson’s disease.
YR 2013
FD 2013
LK http://riull.ull.es/xmlui/handle/915/38566
UL http://riull.ull.es/xmlui/handle/915/38566
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 17-sep-2024