Induction of corticostriatal LTP by 3-nitropropionic acid requires the activation of mGluR1/PKC pathway.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder typically affecting individuals in midlife. HD is characterized by the selective loss of striatal spiny neurons, while large cholinergic interneurons are spared. An impaired mitochondrial complex II (succinate dehydrogenase, SD) activity is known as a prominent metabolic alteration in HD. Accordingly, chronic treatment with 3-nitropropionic acid (3-NP), an irreversible SD inhibitor, mimics motor abnormalities and pathology of HD in several animal models. We have previously shown that in vitro application of 3-NP induces a long-term potentiation (LTP) of corticostriatal synaptic transmission through NMDA glutamate receptor. Since this 3-NP-induced LTP (3-NP-LTP) is shown by striatal spiny neurons, but not by cholinergic interneurons, it might play a role in the regional and cell type-specific neuronal death observed in HD. Here we investigate the role of group I metabotropic glutamate receptors (mGluRs) in the induction of 3-NP-LTP. We report that selectively blocking mGluR1, but not mGluR5, suppresses 3-NP-LTP induction. Moreover, we show that a PKC-mediated mechanism is involved in the formation of 3-NP-LTP. Characterizing the cellular mechanisms underlying 3-NP-LTP may provide new insights to better understand the processes leading to the selective neuronal loss observed in HD.
Gubellini
Paolo
P
Interactions Cellulaires, Neurodégénérescence et Neuroplasticité (IC2N), CNRS, 13402 Marseille Cedex 20, France. paolo.gubellini@ncf.cnrsrs.fr
Centonze
Diego
D
Tropepi
Domenicantonio
D
Bernardi
Giorgio
G
Calabresi
Paolo
P
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009574:Nitro Compounds; D011422:Propionates / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D009574:Nitro Compounds; D011422:Propionates; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D011493:Protein Kinase C; C015392:3-nitropropionic acid