A marked decrease in the activity of mitochondrial complex II (succinate dehydrogenase, SD) has been found in the brains of Huntington's disease (HD) patients. Here we have examined the possibility that SD inhibitors might produce their toxic action by increasing corticostriatal glutamatergic transmission. We report that SD inhibitors produce a durable augmentation of NMDA-mediated corticostriatal excitation (DANCE) in striatal spiny neurons, but not in striatal cholinergic interneurons. DANCE involves increased intracellular calcium, activation of MAP kinase ERK and is critically dependent upon endogenous dopamine (DA) acting via D2-like receptors. This pathological form of corticostriatal synaptic plasticity might play a key role in the regional and cell-type specific neuronal death observed in HD.
Centonze, D., Gubellini, P., Picconi, B., Saulle, E., Tolu, M., Bonsi, P., et al. (2001). An abnormal striatal synaptic plasticity may account for the selective neuronal vulnerability in Huntington's disease. NEUROLOGICAL SCIENCES, 22(1), 61-62 [10.1007/s100720170047].
An abnormal striatal synaptic plasticity may account for the selective neuronal vulnerability in Huntington's disease
CENTONZE, DIEGO;CALABRESI, PAOLO
2001-02-01
Abstract
A marked decrease in the activity of mitochondrial complex II (succinate dehydrogenase, SD) has been found in the brains of Huntington's disease (HD) patients. Here we have examined the possibility that SD inhibitors might produce their toxic action by increasing corticostriatal glutamatergic transmission. We report that SD inhibitors produce a durable augmentation of NMDA-mediated corticostriatal excitation (DANCE) in striatal spiny neurons, but not in striatal cholinergic interneurons. DANCE involves increased intracellular calcium, activation of MAP kinase ERK and is critically dependent upon endogenous dopamine (DA) acting via D2-like receptors. This pathological form of corticostriatal synaptic plasticity might play a key role in the regional and cell-type specific neuronal death observed in HD.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
