RT Journal Article
SR Electronic
T1 Inhibition of Mitochondrial Complex II Induces a Long-Term Potentiation of NMDA-Mediated Synaptic Excitation in the Striatum Requiring Endogenous Dopamine
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5110
OP 5120
DO 10.1523/JNEUROSCI.21-14-05110.2001
VO 21
IS 14
A1 Paolo Calabresi
A1 Paolo Gubellini
A1 Barbara Picconi
A1 Diego Centonze
A1 Antonio Pisani
A1 Paola Bonsi
A1 Paul Greengard
A1 Robert A. Hipskind
A1 Emiliana Borrelli
A1 Giorgio Bernardi
YR 2001
UL http://www.jneurosci.org/content/21/14/5110.abstract
AB Abnormal involuntary movements and cognitive impairment represent the classical clinical symptoms of Huntington's disease (HD). This genetic disorder involves degeneration of striatal spiny neurons, but not striatal large cholinergic interneurons, and corresponds to a marked decrease in the activity of mitochondrial complex II [succinate dehydrogenase (SD)] in the brains of HD patients. Here we have examined the possibility that SD inhibitors exert their toxic action by increasing glutamatergic transmission. We report that SD inhibitors such as 3-nitroproprionic acid (3-NP), but not an inhibitor of mitochondrial complex I, produce a long-term potentiation of the NMDA-mediated synaptic excitation (3-NP-LTP) in striatal spiny neurons. In contrast, these inhibitors had no effect on excitatory synaptic transmission in striatal cholinergic interneurons and pyramidal cortical neurons. 3-NP-LTP involves increased intracellular calcium and activation of the mitogen-activated protein kinase extracellular signal-regulated kinase and is critically dependent on endogenous dopamine acting via D2 receptors, whereas it is negatively regulated by D1 receptors. Thus 3-NP-LTP might play a key role in the regional and cell type-specific neuronal death observed in HD.