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 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 (39) Citing Articles via Google Scholar Google Scholar Articles by Tillerson, J. L. Articles by Miller, G. W. Search for Related Content PubMed PubMed Citation Articles by Tillerson, J. L. Articles by Miller, G. W.

 Previous Article  |  Next Article 

The Journal of Neuroscience, August 1, 2002, 22(15):6790-6799

Forced Nonuse in Unilateral Parkinsonian Rats Exacerbates Injury

Jennifer L. Tillerson¹, Ann D. Cohen³, W. Michael Caudle², Michael J. Zigmond³, Timothy Schallert^{1, 4}, and Gary W. Miller^{1, 2}

¹ Institute for Neuroscience and ² Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, ³ Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, and ⁴ Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan 48109

Diagnosis of Parkinson's disease (PD) is based on the presentation of clinical symptoms such as bradykinesia, resting tremor, and rigidity. However, one feature of PD that often begins years before diagnosis is decreased physical activity. We hypothesized that this depressed activity is not only a symptom of the early dopaminergic loss but also a catalyst in the degenerative process. Two experiments were performed to test this hypothesis. First, rats were exposed to a mild dose of 6-hydroxydopamine unilaterally into the nigrostriatal dopamine (DA) projections, which would normally result in an ~20% DA loss and no detectable behavioral asymmetries. A subset of these lesioned animals then had a cast applied for 7 d to the contralateral forelimb. After the cast was removed, these animals displayed long-term behavioral asymmetry and exacerbation of neurochemical loss (~60% depletion). Second, a group of animals received a high dose of 6-hydroxydopamine that normally would yield a severe loss of nigrostriatal terminals (~90% loss) and chronic sensorimotor deficits. During the first 7 d after neurotoxin exposure, a subset of these animals were forced to rely on the contralateral forelimb, a procedure we have previously reported to protect DA terminals and behavioral function. Some of these rats then had the use of their "recovered" forelimb restricted during the second or third week after lesioning. This precipitated a severe and chronic loss of DA terminals and functional deficits. These results suggest decreased physical activity not only is a symptom of PD but also may act to potentiate the underlying degeneration.

Key words: Parkinson's disease; physical activity; dopamine; plasticity; dopamine transporter; vesicular monoamine transporter

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/22156790-10$05.00/0

This article has been cited by other articles:

				T. Bordia, C. Campos, L. Huang, and M. Quik Continuous and Intermittent Nicotine Treatment Reduces L-3,4-Dihydroxyphenylalanine (L-DOPA)-Induced Dyskinesias in a Rat Model of Parkinson's Disease J. Pharmacol. Exp. Ther., October 1, 2008; 327(1): 239 - 247. [Abstract] [Full Text] [PDF]

				Y. Hayashi, M. Yoshida, M. Yamato, T. Ide, Z. Wu, M. Ochi-Shindou, T. Kanki, D. Kang, K. Sunagawa, H. Tsutsui, et al. Reverse of Age-Dependent Memory Impairment and Mitochondrial DNA Damage in Microglia by an Overexpression of Human Mitochondrial Transcription Factor A in Mice J. Neurosci., August 20, 2008; 28(34): 8624 - 8634. [Abstract] [Full Text] [PDF]

				M A Hirsch and F M Hammond Cueing training in persons with Parkinson's disease J. Neurol. Neurosurg. Psychiatry, February 1, 2007; 78(2): 111 - 111. [Full Text] [PDF]

				S. Jain, J. P. Golden, D. Wozniak, E. Pehek, E. M. Johnson Jr, and J. Milbrandt RET Is Dispensable for Maintenance of Midbrain Dopaminergic Neurons in Adult Mice J. Neurosci., October 25, 2006; 26(43): 11230 - 11238. [Abstract] [Full Text] [PDF]

				M. E Morris Locomotor Training in People With Parkinson Disease Physical Therapy, October 1, 2006; 86(10): 1426 - 1435. [Abstract] [Full Text] [PDF]

				S. M. Fleming, J. Salcedo, P.-O. Fernagut, E. Rockenstein, E. Masliah, M. S. Levine, and M.-F. Chesselet Early and Progressive Sensorimotor Anomalies in Mice Overexpressing Wild-Type Human {alpha}-Synuclein J. Neurosci., October 20, 2004; 24(42): 9434 - 9440. [Abstract] [Full Text] [PDF]

				D. I. Carrasco, M. M. Rich, Q. Wang, T. C. Cope, and M. J. Pinter Activity-Driven Synaptic and Axonal Degeneration in Canine Motor Neuron Disease J Neurophysiol, August 1, 2004; 92(2): 1175 - 1181. [Abstract] [Full Text] [PDF]

				E. Bezard, S. Dovero, D. Belin, S. Duconger, V. Jackson-Lewis, S. Przedborski, P. V. Piazza, C. E. Gross, and M. Jaber Enriched Environment Confers Resistance to 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine and Cocaine: Involvement of Dopamine Transporter and Trophic Factors J. Neurosci., December 3, 2003; 23(35): 10999 - 11007. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help