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 (37) Citing Articles via Google Scholar Google Scholar Articles by Mittoux, V. Articles by Hantraye, P. Search for Related Content PubMed PubMed Citation Articles by Mittoux, V. Articles by Hantraye, P.

 Previous Article  |  Next Article 

The Journal of Neuroscience, June 1, 2002, 22(11):4478-4486

Corticostriatopallidal Neuroprotection by Adenovirus-Mediated Ciliary Neurotrophic Factor Gene Transfer in a Rat Model of Progressive Striatal Degeneration

Vincent Mittoux^{1, *}, Stéphane Ouary^{1, *}, Christelle Monville², Fabrice Lisovoski², Thomas Poyot¹, Françoise Condé¹, Carole Escartin¹, Régine Robichon², Emmanuel Brouillet¹, Marc Peschanski², and Philippe Hantraye^{1, 3}

¹ Unité de Recherche Associée 2210, Commissariat à l'Energie Atomique, Centre National de la Recherche Scientifique, Service Hospitalier Frédéric Joliot, 91401 Orsay Cedex, France, ² Institut National de la Santé et de la Recherche Médicale U421, Institut Mondor de Médecine Moléculaire, Faculté de Médecine, 94010 Créteil Cedex, France, and ³ Unité d'Imagerie Isotopique, Biochimique, et Pharmacologique, Service Hospitalier Frédéric Joliot, Département de la Recherche Médicale, Commissariat à l'Energie Atomique, 91401 Orsay Cedex, France

Ciliary neurotrophic factor (CNTF) is a potent protective factor for striatal neurons in animal models of Huntington's disease (HD). Clinical application of this potential therapeutic still requires the design and optimization of delivery systems. In the case of HD, spatial spread in the vast volume occupied by the striatum and long-term delivery of the factor are particular challenges for these systems. We explored the potential of adenovirus-mediated gene transfer to fulfill these requirements by studying the functional and anatomical effects of single-site striatal delivery of CNTF recombinant vectors in a rat model of HD. In an initial series of experiments, unilateral injections of CNTF adenovirus were performed in rats 10, 30, or 90 d before a 5 d neurotoxic treatment with systemic 3-nitropropionic acid (3NP). Preservation of striatal neurons was observed at all time points, demonstrating temporally extended neuroprotective effects of the CNTF adenovirus. In a second series of experiments, bilateral injections of CNTF adenovirus were performed in the medial aspect of the striatum 10 d before starting 3NP intoxication. Despite placement of the CNTF-producing vector outside the lateral striatal area susceptible to lesion, massive protection of corticostriatopallidal circuits was observed, associated with significant behavioral benefits. This spatial spread of neuroprotection is discussed with reference to the retrograde transport of the adenovirus vector and the anterograde transport of the transgenic CNTF. Overall, adenovirus-mediated CNTF gene transfer appears to be a potentially useful delivery system for widespread, long-term circuit neuroprotection in HD patients.

Key words: adenovirus vector; ciliary neurotrophic factor; 3-nitropropionic acid; corticostriatopallidal degeneration; neuroprotection; rat; stereology; Huntington's disease

---

^* V.M. and S.O. contributed equally to this work.

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/22114478-09$05.00/0

This article has been cited by other articles:

				C. Escartin, K. Pierre, A. Colin, E. Brouillet, T. Delzescaux, M. Guillermier, M. Dhenain, N. Deglon, P. Hantraye, L. Pellerin, et al. Activation of Astrocytes by CNTF Induces Metabolic Plasticity and Increases Resistance to Metabolic Insults J. Neurosci., July 4, 2007; 27(27): 7094 - 7104. [Abstract] [Full Text] [PDF]

				T. M. Woodruff, J. W. Crane, L. M. Proctor, K. M. Buller, A. B. Shek, K. de Vos, S. Pollitt, H. M. Williams, I. A. Shiels, P. N. Monk, et al. Therapeutic activity of C5a receptor antagonists in a rat model of neurodegeneration FASEB J, July 1, 2006; 20(9): 1407 - 1417. [Abstract] [Full Text] [PDF]

				C. Escartin, E. Brouillet, P. Gubellini, Y. Trioulier, C. Jacquard, C. Smadja, G. W. Knott, L. K.-L. Goff, N. Deglon, P. Hantraye, et al. Ciliary neurotrophic factor activates astrocytes, redistributes their glutamate transporters GLAST and GLT-1 to raft microdomains, and improves glutamate handling in vivo. J. Neurosci., May 31, 2006; 26(22): 5978 - 5989. [Abstract] [Full Text] [PDF]

				M. Peschanski, A.-C. Bachoud-Levi, and P. Hantraye Integrating fetal neural transplants into a therapeutic strategy: the example of Huntington's disease Brain, June 1, 2004; 127(6): 1219 - 1228. [Abstract] [Full Text] [PDF]

				N. Bizat, J.-M. Hermel, S. Humbert, C. Jacquard, C. Creminon, C. Escartin, F. Saudou, S. Krajewski, P. Hantraye, and E. Brouillet In Vivo Calpain/Caspase Cross-talk during 3-Nitropropionic Acid-induced Striatal Degeneration: IMPLICATION OF A CALPAIN-MEDIATED CLEAVAGE OF ACTIVE CASPASE-3 J. Biol. Chem., October 31, 2003; 278(44): 43245 - 43253. [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, D. Gall, M.-C. Galas, P. d'Alcantara, K. Bantubungi, and S. N. Schiffmann The Adenosine A1 Receptor Agonist Adenosine Amine Congener Exerts a Neuroprotective Effect against the Development of Striatal Lesions and Motor Impairments in the 3-Nitropropionic Acid Model of Neurotoxicity J. Neurosci., October 15, 2002; 22(20): 9122 - 9133. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help