QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (89) Citing Articles via Google Scholar Google Scholar Articles by Calabresi, P. Articles by Bernardi, G. Search for Related Content PubMed PubMed Citation Articles by Calabresi, P. Articles by Bernardi, G.

 Previous Article  |  Next Article 

The Journal of Neuroscience, July 15, 2001, 21(14):5110-5120

Inhibition of Mitochondrial Complex II Induces a Long-Term Potentiation of NMDA-Mediated Synaptic Excitation in the Striatum Requiring Endogenous Dopamine

Paolo Calabresi^{1, 2}, Paolo Gubellini^{1, 3}, Barbara Picconi^{1, 2}, Diego Centonze^{1, 2}, Antonio Pisani^{1, 2}, Paola Bonsi^{1, 2}, Paul Greengard⁴, Robert A. Hipskind⁵, Emiliana Borrelli⁶, and Giorgio Bernardi^{1, 2}

¹ Clinica Neurologica, Dipartimento di Neuroscienze, Università di "Tor Vergata," Rome 00133, Italy, ² Fondazione Santa Lucia IRCCS, Rome 00179, Italy, ³ Istituto di Neuroscienze e Medicina Molecolare, Consiglio Nazionale delle Ricerche, Rome 00133, Italy, ⁴ Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York 10021, New York, ⁵ Institut de Génétique Moléculaire, Centre National de la Recherche Scientifique (CNRS)-Unité Mixte de Recherche 5535, Montpellier 34293, France, and ⁶ Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS-Institut National de la Santé et de la Recherche Médicale-ULP, CU de Strasbourg 67404, France

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.

Key words: D2 dopamine receptors; Huntington's disease; striatum; succinate dehydrogenase; synaptic plasticity; excitotoxicity

---

Copyright © 2001 Society for Neuroscience  0270-6474/01/21145110-11$05.00/0

This article has been cited by other articles:

				G. Akopian, C. Crawford, M. F. Beal, M. Cappelletti, M. W. Jakowec, G. M. Petzinger, L. Zheng, S. L. Gheorghe, C. M. Reichel, R. Chow, et al. Decreased Striatal Dopamine Release Underlies Increased Expression of Long-Term Synaptic Potentiation at Corticostriatal Synapses 24 h after 3-Nitropropionic-Acid-Induced Chemical Hypoxia J. Neurosci., September 17, 2008; 28(38): 9585 - 9597. [Abstract] [Full Text] [PDF]

				C. Costa, V. Belcastro, A. Tozzi, M. Di Filippo, M. Tantucci, S. Siliquini, A. Autuori, B. Picconi, M. G. Spillantini, E. Fedele, et al. Electrophysiology and Pharmacology of Striatal Neuronal Dysfunction Induced by Mitochondrial Complex I Inhibition J. Neurosci., August 6, 2008; 28(32): 8040 - 8052. [Abstract] [Full Text] [PDF]

				E. C. Stack, A. Dedeoglu, K. M. Smith, K. Cormier, J. K. Kubilus, M. Bogdanov, W. R. Matson, L. Yang, B. G. Jenkins, R. Luthi-Carter, et al. Neuroprotective Effects of Synaptic Modulation in Huntington's Disease R6/2 Mice J. Neurosci., November 21, 2007; 27(47): 12908 - 12915. [Abstract] [Full Text] [PDF]

				T. Milakovic, R. A. Quintanilla, and G. V. W. Johnson Mutant Huntingtin Expression Induces Mitochondrial Calcium Handling Defects in Clonal Striatal Cells: FUNCTIONAL CONSEQUENCES J. Biol. Chem., November 17, 2006; 281(46): 34785 - 34795. [Abstract] [Full Text] [PDF]

				A. Solans, A. Zambrano, M. Rodriguez, and A. Barrientos Cytotoxicity of a mutant huntingtin fragment in yeast involves early alterations in mitochondrial OXPHOS complexes II and III Hum. Mol. Genet., October 15, 2006; 15(20): 3063 - 3081. [Abstract] [Full Text] [PDF]

				J. M. Paterson, D. Short, P. W. Flatman, J. R. Seckl, A. Aitken, and M. B. Dutia Changes in protein expression in the rat medial vestibular nuclei during vestibular compensation J. Physiol., September 15, 2006; 575(3): 777 - 788. [Abstract] [Full Text] [PDF]

				C. Jacquard, Y. Trioulier, F. Cosker, C. Escartin, N. Bizat, P. Hantraye, J. M. Cancela, G. Bonvento, and E. Brouillet Brain mitochondrial defects amplify intracellular [Ca2+] rise and neurodegeneration but not Ca2+ entry during NMDA receptor activation FASEB J, May 1, 2006; 20(7): 1021 - 1023. [Abstract] [Full Text] [PDF]

				S. W. Perry, J. P. Norman, A. Litzburg, D. Zhang, S. Dewhurst, and H. A. Gelbard HIV-1 Transactivator of Transcription Protein Induces Mitochondrial Hyperpolarization and Synaptic Stress Leading to Apoptosis J. Immunol., April 1, 2005; 174(7): 4333 - 4344. [Abstract] [Full Text] [PDF]

				H. Ardehali, Z. Chen, Y. Ko, R. Mejia-Alvarez, and E. Marban Multiprotein complex containing succinate dehydrogenase confers mitochondrial ATP-sensitive K+ channel activity PNAS, August 10, 2004; 101(32): 11880 - 11885. [Abstract] [Full Text] [PDF]

				Y. Wang, S. L. Chan, L. Miele, P. J. Yao, J. Mackes, D. K. Ingram, M. P. Mattson, and K. Furukawa Involvement of Notch signaling in hippocampal synaptic plasticity PNAS, June 22, 2004; 101(25): 9458 - 9462. [Abstract] [Full Text] [PDF]

				N. Brustovetsky, T. Brustovetsky, K. J. Purl, M. Capano, M. Crompton, and J. M. Dubinsky Increased Susceptibility of Striatal Mitochondria to Calcium-Induced Permeability Transition J. Neurosci., June 15, 2003; 23(12): 4858 - 4867. [Abstract] [Full Text] [PDF]

				N. Bizat, J.-M. Hermel, F. Boyer, C. Jacquard, C. Creminon, S. Ouary, C. Escartin, P. Hantraye, S. Kajewski, and E. Brouillet Calpain Is a Major Cell Death Effector in Selective Striatal Degeneration Induced In Vivo by 3-Nitropropionate: Implications for Huntington's Disease J. Neurosci., June 15, 2003; 23(12): 5020 - 5030. [Abstract] [Full Text] [PDF]

				D. Blum, M.-C. Galas, A. Pintor, E. Brouillet, C. Ledent, C. E. Muller, K. Bantubungi, M. Galluzzo, D. Gall, L. Cuvelier, et al. A Dual Role of Adenosine A2A Receptors in 3-Nitropropionic Acid-Induced Striatal Lesions: Implications for the Neuroprotective Potential of A2A Antagonists J. Neurosci., June 15, 2003; 23(12): 5361 - 5369. [Abstract] [Full Text] [PDF]

				C. Cepeda, R. S. Hurst, C. R. Calvert, E. Hernandez-Echeagaray, O. K. Nguyen, E. Jocoy, L. J. Christian, M. A. Ariano, and M. S. Levine Transient and Progressive Electrophysiological Alterations in the Corticostriatal Pathway in a Mouse Model of Huntington's Disease J. Neurosci., February 1, 2003; 23(3): 961 - 969. [Abstract] [Full Text] [PDF]

				J. C. Liu, R. E. Baker, C. Sun, V. C. Sundmark, and H. P. Elsholtz Activation of Go-coupled Dopamine D2 Receptors Inhibits ERK1/ERK2 in Pituitary Cells. A KEY STEP IN THE TRANSCRIPTIONAL SUPPRESSION OF THE PROLACTIN GENE J. Biol. Chem., September 20, 2002; 277(39): 35819 - 35825. [Abstract] [Full Text] [PDF]

				P. Gubellini, B. Picconi, M. Bari, N. Battista, P. Calabresi, D. Centonze, G. Bernardi, A. Finazzi-Agro, and M. Maccarrone Experimental Parkinsonism Alters Endocannabinoid Degradation: Implications for Striatal Glutamatergic Transmission J. Neurosci., August 15, 2002; 22(16): 6900 - 6907. [Abstract] [Full Text] [PDF]

				C. M. Maier and P. H. Chan Book Review: Role of Superoxide Dismutases in Oxidative Damage and Neurodegenerative Disorders Neuroscientist, August 1, 2002; 8(4): 323 - 334. [Abstract] [PDF]

				P. Calabresi, E. Saulle, D. Centonze, A. Pisani, G. A. Marfia, and G. Bernardi Post-ischaemic long-term synaptic potentiation in the striatum: a putative mechanism for cell type-specific vulnerability Brain, April 1, 2002; 125(4): 844 - 860. [Abstract] [Full Text] [PDF]

				S Davies and D B Ramsden Huntington's disease Mol. Pathol., December 1, 2001; 54(6): 409 - 413. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help