An abnormal striatal synaptic plasticity may account for the selective neuronal vulnerability in Huntington's disease |
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| Authors: | D Centonze P Gubellini B Picconi E Saulle M Tolu P Bonsi P Giacomini P Calabresi |
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| Institution: | (1) Neurology Clinic, Neurosciences Department, University of Rome Tor Vergata, Via di Tor Vergata 135, I-00133 Rome, Italy and Fondazione Santa Lucia, Rome, Italy, IT;(2) Neurology Clinic II, University of Rome La Sapienza, Rome, Italy, IT |
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| 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. |
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