An impaired complex II (succinate dehydrogenase, SD) striatal mitochondrial activity is one of the prominent metabolic alterations in Huntington's disease (HD), and intoxication with 3-nitropropionic acid (3-NP), an inhibitor of mitochondrial complex II, mimics the motor abnormalities and the pathology of HD. We found that striatal spiny neurons responded to this toxin with an irreversible membrane depolarization/inward current, while cholinergic interneurons showed a hyperpolarization/outward current. Both these currents were sensitive to intracellular concentration of ATP. The 3-NP-induced depolarization was associated with an increased release of endogenous GABA, while acetylcholine levels were reduced. Moreover, 3-NP induced a higher depolarization in presymptomatic R6/2 HD transgenic mice compared to wild-type (WT) mice, showing an increased susceptibility to SD inhibition. Conversely, the hyperpolarization did not significantly differ from the one recorded in WT mice. The diverse membrane changes induced by SD inhibition may contribute to the cell-type-specific neuronal death in HD.

Saulle, E., Gubellini, P., Picconi, B., Centonze, D., Tropepi, D., Pisani, A., et al. (2004). Neuronal vulnerability following inhibition of mitochondrial complex II: a possibile ionic mechanism for Huntington’s disease. MOLECULAR AND CELLULAR NEUROSCIENCES, 25(1), 9-20 [doi:10.1016/j.mcn.2003.09.013].

Neuronal vulnerability following inhibition of mitochondrial complex II: a possibile ionic mechanism for Huntington’s disease.

CENTONZE, DIEGO;PISANI, ANTONIO;ROSSI, LUISA;BERNARDI, GIORGIO;CALABRESI, PAOLO
2004-01-01

Abstract

An impaired complex II (succinate dehydrogenase, SD) striatal mitochondrial activity is one of the prominent metabolic alterations in Huntington's disease (HD), and intoxication with 3-nitropropionic acid (3-NP), an inhibitor of mitochondrial complex II, mimics the motor abnormalities and the pathology of HD. We found that striatal spiny neurons responded to this toxin with an irreversible membrane depolarization/inward current, while cholinergic interneurons showed a hyperpolarization/outward current. Both these currents were sensitive to intracellular concentration of ATP. The 3-NP-induced depolarization was associated with an increased release of endogenous GABA, while acetylcholine levels were reduced. Moreover, 3-NP induced a higher depolarization in presymptomatic R6/2 HD transgenic mice compared to wild-type (WT) mice, showing an increased susceptibility to SD inhibition. Conversely, the hyperpolarization did not significantly differ from the one recorded in WT mice. The diverse membrane changes induced by SD inhibition may contribute to the cell-type-specific neuronal death in HD.
2004
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/10 - BIOCHIMICA
English
Con Impact Factor ISI
Saulle, E., Gubellini, P., Picconi, B., Centonze, D., Tropepi, D., Pisani, A., et al. (2004). Neuronal vulnerability following inhibition of mitochondrial complex II: a possibile ionic mechanism for Huntington’s disease. MOLECULAR AND CELLULAR NEUROSCIENCES, 25(1), 9-20 [doi:10.1016/j.mcn.2003.09.013].
Saulle, E; Gubellini, P; Picconi, B; Centonze, D; Tropepi, D; Pisani, A; Morari, M; Marti, M; Rossi, L; Papa, M; Bernardi, G; Calabresi, P
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/32989
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