Neurological Sciences

, Volume 22, Issue 1, pp 61-62

An abnormal striatal synaptic plasticity may account for the selective neuronal vulnerability in Huntington's disease

  • D. CentonzeAffiliated withNeurology Clinic, Neurosciences Department, University of Rome Tor Vergata, Via di Tor Vergata 135, I-00133 Rome, Italy and Fondazione Santa Lucia, Rome, Italy
  • , P. GubelliniAffiliated withNeurology Clinic, Neurosciences Department, University of Rome Tor Vergata, Via di Tor Vergata 135, I-00133 Rome, Italy and Fondazione Santa Lucia, Rome, Italy
  • , B. PicconiAffiliated withNeurology Clinic, Neurosciences Department, University of Rome Tor Vergata, Via di Tor Vergata 135, I-00133 Rome, Italy and Fondazione Santa Lucia, Rome, Italy
  • , E. SaulleAffiliated withNeurology Clinic, Neurosciences Department, University of Rome Tor Vergata, Via di Tor Vergata 135, I-00133 Rome, Italy and Fondazione Santa Lucia, Rome, Italy
  • , M. ToluAffiliated withNeurology Clinic, Neurosciences Department, University of Rome Tor Vergata, Via di Tor Vergata 135, I-00133 Rome, Italy and Fondazione Santa Lucia, Rome, Italy
  • , P. BonsiAffiliated withNeurology Clinic, Neurosciences Department, University of Rome Tor Vergata, Via di Tor Vergata 135, I-00133 Rome, Italy and Fondazione Santa Lucia, Rome, Italy
  • , P. GiacominiAffiliated withNeurology Clinic II, University of Rome La Sapienza, Rome, Italy
  • , P. CalabresiAffiliated withNeurology Clinic, Neurosciences Department, University of Rome Tor Vergata, Via di Tor Vergata 135, I-00133 Rome, Italy and Fondazione Santa Lucia, Rome, Italy

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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.