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02-28-2007, 11:58 AM | #1 | |||
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Osteopontin is elevated in Parkinson’s disease and its absence leads to reduced neurodegeneration in the MPTP model
Walter Maetzlera, , , Daniela Berga, Natalie Schalamberidzea, Arthur Melmsb, Klaus Schottc, Jakob C. Muellera, d, Lucy Liawe, Thomas Gassera and Cordula Nitschf aHertie Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tuebingen, Otfried-Mueller Strasse 27, 72076 Tuebingen, Germany bDepartment of General Neurology, University of Tuebingen, Germany cDepartment of Psychiatry and Psychotherapy, University of Tuebingen, Germany dInstitute for Med. Statistics and Epidem. and Institute for Psychiatry and Psychotherapy, Technical University, Munich, Germany eCenter for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, USA fSection of Functional Neuroanatomy, Dept. Clinical-Biological Sciences, University of Basel, Switzerland Received 18 August 2006; revised 19 October 2006; accepted 29 October 2006. Available online 26 December 2006. Abstract In the pathogenesis of Parkinson’s disease (PD), oxidative and nitrosative stress, apoptosis, mitochondrial dysfunction, and excitotoxicity are involved, i.e., processes in which osteopontin (OPN) may also play a role. We have studied in PD patients serum and cerebrospinal fluid (CSF) concentrations of OPN, its immunohistochemical presence in substantia nigra (SN) and tested in OPN-null mice the impact of this protein on MPTP-induced neurodegeneration. PD was accompanied by increased OPN levels in the body fluids. Higher serum levels were associated with more severe motor symptoms. CSF levels were positively associated with concomitant dementia and negatively associated with dopaminergic treatment. In human SN, OPN was expressed in neurons, in their Lewy bodies and in microglia. Loss of tyrosine-hydroxylase-positive cells in the SN and of dopaminergic fibers in the striatum was reduced 3 weeks after MPTP intoxication in OPN-null mice. These data suggest that OPN is involved in PD-associated neurodegeneration. Keywords: Cerebrospinal fluid; Dementia; Hoehn and Yahr; Osteopontin-null mice; Serum Corresponding author. Fax: +49 7071 294620. |
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