Osteopontin is elevated in Parkinson's disease and its absence leads to reduced neurodegeneration in the MPTP model.
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.
Maetzler
Walter
W
Hertie Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tuebingen, Otfried-Mueller Strasse 27, 72076 Tuebingen, Germany. walter.maetzler@un-tuebingen.de
Berg
Daniela
D
Schalamberidze
Natalie
N
Melms
Arthur
A
Schott
Klaus
K
Mueller
Jakob C
JC
Liaw
Lucy
L
Gasser
Thomas
T
Nitsch
Cordula
C
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008875:Middle Aged; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D053495:Osteopontin / Q000097:blood* / Q000134:cerebrospinal fluid; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000473:pathology; D012720:Severity of Illness Index; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology
D053495:Osteopontin; D004298:Dopamine