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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, February 25, 2004, 24(8):2045-2053; doi:10.1523/JNEUROSCI.4564-03.2004

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 ISI 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 ISI Web of Science (37) Citing Articles via Google Scholar Google Scholar Articles by Hayley, S. Articles by Park, D. S. Search for Related Content PubMed PubMed Citation Articles by Hayley, S. Articles by Park, D. S.

 Previous Article  |  Next Article 

Neurobiology of Disease
Regulation of Dopaminergic Loss by Fas in a 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Model of Parkinson's Disease

Shawn Hayley,^1,3 Stephen J. Crocker,¹ Patrice D. Smith,¹ Tanaya Shree,¹ Vernice Jackson-Lewis,² Serge Przedborski,² Matthew Mount,¹ Ruth Slack,¹ Hymie Anisman,³ and David S. Park¹

¹Ottawa Health Research Institute, Neuroscience Group, Ottawa, Ontario, Canada K1H 8M5, ²The Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, and ³Institute of Neuroscience, Carleton University, Ottawa, Ontario, Canada K1S 5B6

Accumulating evidence suggests that apoptotic and inflammatory factors contribute to the demise of dopaminergic neurons. In this respect, Fas, a member of the tumor necrosis factor receptor family with proapoptotic and inflammatory functions, was reported to be elevated within the striatum and substantia nigra pars compacta (SNc) of Parkinson's disease (PD) patients. Accordingly, the present investigation evaluated the function of Fas in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. Injection of MPTP increased nigral Fas expression, and mice lacking Fas displayed attenuated MPTP-induced SNc dopaminergic loss and microglial activation. In addition, Fas induction was blocked by expression of a dominant-negative c-Jun adenovirus that also protected dopamine neurons from MPTP-induced damage. Together, these data suggest the critical nature of the c-Jun-Fas signaling pathway in MPTP-induced neuronal loss. Although critical for degeneration of the soma, Fas deficiency did not significantly prevent the reduction of dopaminergic terminal fibers within the striatum or normalize the activation of striatal microglia and elevation of the postsynaptic activity marker FosB induced by denervation. Interestingly, Fas-deficient mice displayed a pre-existing reduction in striatal dopamine levels and locomotor behavior when compared with wild-type mice. Despite the reduced terminals, dopamine levels were not further suppressed by MPTP treatment in mutant mice, raising the possibility of a compensatory response in basal ganglia function in Fas-deficient mice.

Key words: Fas; neurodegeneration; cytokine; kinase; stress; dopamine

---

Received Oct 8, 2003; revised December 19, 2003; accepted December 27, 2003.

This article has been cited by other articles:

				X. Chen, M. Rzhetskaya, T. Kareva, R. Bland, M. J. During, A. W. Tank, N. Kholodilov, and R. E. Burke Antiapoptotic and Trophic Effects of Dominant-Negative Forms of Dual Leucine Zipper Kinase in Dopamine Neurons of the Substantia Nigra In Vivo J. Neurosci., January 16, 2008; 28(3): 672 - 680. [Abstract] [Full Text] [PDF]

				T. Kawasaki, K. Ishihara, Y. Ago, A. Baba, and T. Matsuda Edaravone (3-Methyl-1-phenyl-2-pyrazolin-5-one), a Radical Scavenger, Prevents 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Neurotoxicity in the Substantia Nigra but Not the Striatum J. Pharmacol. Exp. Ther., July 1, 2007; 322(1): 274 - 281. [Abstract] [Full Text] [PDF]

				M. P. Mount, A. Lira, D. Grimes, P. D. Smith, S. Faucher, R. Slack, H. Anisman, S. Hayley, and D. S. Park Involvement of Interferon-{gamma} in Microglial-Mediated Loss of Dopaminergic Neurons J. Neurosci., March 21, 2007; 27(12): 3328 - 3337. [Abstract] [Full Text] [PDF]

				P. D. Smith, M. P. Mount, R. Shree, S. Callaghan, R. S. Slack, H. Anisman, I. Vincent, X. Wang, Z. Mao, and D. S. Park Calpain-Regulated p35/cdk5 Plays a Central Role in Dopaminergic Neuron Death through Modulation of the Transcription Factor Myocyte Enhancer Factor 2 J. Neurosci., January 11, 2006; 26(2): 440 - 447. [Abstract] [Full Text] [PDF]

				A. M. Landau, K. C. Luk, M.-L. Jones, R. Siegrist-Johnstone, Y. K. Young, E. Kouassi, V. V. Rymar, A. Dagher, A. F. Sadikot, and J. Desbarats Defective Fas expression exacerbates neurotoxicity in a model of Parkinson's disease J. Exp. Med., September 6, 2005; 202(5): 575 - 581. [Abstract] [Full Text] [PDF]

				R. H. Kim, P. D. Smith, H. Aleyasin, S. Hayley, M. P. Mount, S. Pownall, A. Wakeham, A. J. You-Ten, S. K. Kalia, P. Horne, et al. Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress PNAS, April 5, 2005; 102(14): 5215 - 5220. [Abstract] [Full Text] [PDF]

				R. M. Miller, L. M. Callahan, C. Casaceli, L. Chen, G. L. Kiser, B. Chui, T. M. Kaysser-Kranich, T. J. Sendera, C. Palaniappan, and H. J. Federoff Dysregulation of Gene Expression in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioned Mouse Substantia Nigra J. Neurosci., August 25, 2004; 24(34): 7445 - 7454. [Abstract] [Full Text] [PDF]

				D. Marazziti, E. Golini, S. Mandillo, A. Magrelli, W. Witke, R. Matteoni, and G. P. Tocchini-Valentini Altered dopamine signaling and MPTP resistance in mice lacking the Parkinson's disease-associated GPR37/parkin-associated endothelin-like receptor PNAS, July 6, 2004; 101(27): 10189 - 10194. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help