title: Forced nonuse in unilateral parkinsonian rats exacerbates injury.
abstract: 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 approximately 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 (approximately 60% depletion). Second, a group of animals received a high dose of 6-hydroxydopamine that normally would yield a severe loss of nigrostriatal terminals (approximately 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.
authors.affiliation: Institute for Neuroscience, University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Tillerson
authors.forename: Ann D
authors.initials: AD
authors.lastname: Cohen
authors.forename: W Michael
authors.initials: WM
authors.lastname: Caudle
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zigmond
authors.forename: Timothy
authors.initials: T
authors.lastname: Schallert
authors.forename: Gary W
authors.initials: GW
authors.lastname: Miller
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002370:Casts, Surgical; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004298:Dopamine / Q000032:analysis; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D005552:Forelimb / Q000503:physiopathology; D006719:Homovanillic Acid / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D026901:Membrane Transport Proteins / Q000032:analysis; D009068:Movement / Q000187:drug effects; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000503:physiopathology*; D005082:Physical Exertion; D051381:Rats; D020318:Rats, Long-Evans; D012149:Restraint, Physical / Q000009:adverse effects*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis; D050492:Vesicular Biogenic Amine Transport Proteins
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D050492:Vesicular Biogenic Amine Transport Proteins; D015102:3,4-Dihydroxyphenylacetic Acid; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D004298:Dopamine; D006719:Homovanillic Acid