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.

Forgive my stupidity, but what is Osteopontin? Is it something to do with Osteoporisis?

Dumbly,
Vicky

LOL I looked it up and couldn't understand a word of it either. I think it's a protein that is bad to have too much of like alpha synuclein.

but don't quote me,
yours in dumbness,
paula

Osteopontin as a Regulator of the Inflammatory Response to Nigral Cell Degeneration....


http://www.michaeljfox.org/research/abstract.php?id=102

OPN is present in the substantia nigra and possesses a range of anti-inflammatory properties.

Increased osteopontin expression following intranigral lipopolysaccharide injection in the rat

* Joanna Iczkiewicz,
* Sarah Rose and
* Peter Jenner

DISCUSSION:

Inflammation is increasingly believed to play a role in the neurodegenerative mechanisms that occur in age-related disorders such as PD (McGeer et al., 1988; Hirsch et al., 2003; Hunot & Hirsch, 2003; McGeer & McGeer, 2004). By manipulating the inflammatory process it may be possible to prevent the progression of nigral dopaminergic cell loss in PD. OPN is a protein that may have a role to play in cell death through its dual pro- and anti-inflammatory functions (Denhardt et al., 2001b; Giachelli & Steitz, 2000). We have previously demonstrated the presence of OPN in the basal ganglia (Iczkiewicz et al., 2004) and, for these reasons, we have investigated whether OPN expression is altered in the primary site of PD pathology, namely the SN, after inflammatory insult. For the first time, we have demonstrated that nigral cell death in the rat SN is accompanied by a rapid induction of OPN mRNA and protein expression after intranigral injection of LPS. Furthermore, we have demonstrated that, in this experimental model, OPN is colocalized with glial cells...........

Inflammation is increasingly believed to play a role in the neurodegenerative mechanisms that occur in age-related disorders such as PD (McGeer et al., 1988; Hirsch et al., 2003; Hunot & Hirsch, 2003; McGeer & McGeer, 2004). By manipulating the inflammatory process it may be possible to prevent the progression of nigral dopaminergic cell loss in PD. OPN is a protein that may have a role to play in cell death through its dual pro- and anti-inflammatory functions (Denhardt et al., 2001b; Giachelli & Steitz, 2000). We have previously demonstrated the presence of OPN in the basal ganglia (Iczkiewicz et al., 2004) and, for these reasons, we have investigated whether OPN expression is altered in the primary site of PD pathology, namely the SN, after inflammatory insult. For the first time, we have demonstrated that nigral cell death in the rat SN is accompanied by a rapid induction of OPN mRNA and protein expression after intranigral injection of LPS. Furthermore, we have demonstrated that, in this experimental model, OPN is colocalized with glial cells.

http://www.blackwell-synergy.com/doi...8.2005.04009.x

Sorry I was in a real hurry this morning. I need to give more info when I do things.

Thanks all