Experimental destruction of substantia nigra initiated by Parkinson disease immunoglobulins

Shengdi Chen, Weidong D. Le, Wenjie J. Xie, Maria E. Alexianu, J. Engelhardt, L. Siklós, Stanley H. Appel

Research output: Contribution to journalArticle

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Abstract

Background: Increased levels of free radicals and oxidative stress may contribute to the pathogenesis of substantia nigra (SN) injury in Parkinson disease (PD), but the initiating etiologic factors remain undefined in most cases. Objective: To determine the potential importance of immune mechanisms in triggering or amplifying neuronal injury, we assayed serum samples from patients with PD to determine the ability of IgG to initiate relatively specific SN injury in vivo. Methods: IgG purified from the serum of 5 patients with PD and 10 disease control (DC) patients was injected into the right side of the SN in adult rats. Coronal sections were cut from the whole brain at the level of the stereotaxic injections, stained for tyrosine hydroxylase and with cresyl violet, and cellular profiles were counted in identical brain regions at the injection and contralateral sides. The ratio of cell profile counts of the corresponding injected and uninjected regions was used as an internal standard. Results: Four weeks following injection of IgG, a 50% decrease in tyrosine hydroxylase-positive cellular profiles was noted on the injected sides compared with the contralateral sides of the same animals. Similarly, applied DC IgG caused only an 18% decrease. Cresyl violet staining revealed a 35% decrease in neuronal profiles of PD IgG injected into the SN pars compacta compared with the contralateral uninjected side, whereas DC IgG caused a minimal 10% decrease. Even at 4 weeks after the PD IgG injections, perivascular inflammation and significant microglial infiltration were present near injured SN pars compacta neurons. No cytotoxic effects of PD IgG were noted in choline acetyltransferase-positive neurons after stereotaxic injections into the medial septal region. Absorption of PD lgG with mesencephalic membranes and protein A agarose gel beads removed cytotoxicity, while absorption with liver membranes did not change the cytotoxicity. Conclusions: Our data suggest that PD IgG can initiate a relatively specific inflammatory destruction of SN pars compacta neurons in vivo and demonstrate the potential relevance of immune mechanisms in PD.

Original languageEnglish
Pages (from-to)1075-1080
Number of pages6
JournalArchives of Neurology
Volume55
Issue number8
DOIs
Publication statusPublished - Aug 1998

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Substantia Nigra
Parkinson Disease
Immunoglobulins
Immunoglobulin G
Injections
Tyrosine 3-Monooxygenase
Neurons
Wounds and Injuries
Septum of Brain
Parkinson's Disease
Destruction
Choline O-Acetyltransferase
Staphylococcal Protein A
Brain
Serum
Sepharose
Free Radicals
Membrane Proteins
Oxidative Stress
Cell Count

ASJC Scopus subject areas

  • Neuroscience(all)

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Experimental destruction of substantia nigra initiated by Parkinson disease immunoglobulins. / Chen, Shengdi; Le, Weidong D.; Xie, Wenjie J.; Alexianu, Maria E.; Engelhardt, J.; Siklós, L.; Appel, Stanley H.

In: Archives of Neurology, Vol. 55, No. 8, 08.1998, p. 1075-1080.

Research output: Contribution to journalArticle

Chen, Shengdi ; Le, Weidong D. ; Xie, Wenjie J. ; Alexianu, Maria E. ; Engelhardt, J. ; Siklós, L. ; Appel, Stanley H. / Experimental destruction of substantia nigra initiated by Parkinson disease immunoglobulins. In: Archives of Neurology. 1998 ; Vol. 55, No. 8. pp. 1075-1080.
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abstract = "Background: Increased levels of free radicals and oxidative stress may contribute to the pathogenesis of substantia nigra (SN) injury in Parkinson disease (PD), but the initiating etiologic factors remain undefined in most cases. Objective: To determine the potential importance of immune mechanisms in triggering or amplifying neuronal injury, we assayed serum samples from patients with PD to determine the ability of IgG to initiate relatively specific SN injury in vivo. Methods: IgG purified from the serum of 5 patients with PD and 10 disease control (DC) patients was injected into the right side of the SN in adult rats. Coronal sections were cut from the whole brain at the level of the stereotaxic injections, stained for tyrosine hydroxylase and with cresyl violet, and cellular profiles were counted in identical brain regions at the injection and contralateral sides. The ratio of cell profile counts of the corresponding injected and uninjected regions was used as an internal standard. Results: Four weeks following injection of IgG, a 50{\%} decrease in tyrosine hydroxylase-positive cellular profiles was noted on the injected sides compared with the contralateral sides of the same animals. Similarly, applied DC IgG caused only an 18{\%} decrease. Cresyl violet staining revealed a 35{\%} decrease in neuronal profiles of PD IgG injected into the SN pars compacta compared with the contralateral uninjected side, whereas DC IgG caused a minimal 10{\%} decrease. Even at 4 weeks after the PD IgG injections, perivascular inflammation and significant microglial infiltration were present near injured SN pars compacta neurons. No cytotoxic effects of PD IgG were noted in choline acetyltransferase-positive neurons after stereotaxic injections into the medial septal region. Absorption of PD lgG with mesencephalic membranes and protein A agarose gel beads removed cytotoxicity, while absorption with liver membranes did not change the cytotoxicity. Conclusions: Our data suggest that PD IgG can initiate a relatively specific inflammatory destruction of SN pars compacta neurons in vivo and demonstrate the potential relevance of immune mechanisms in PD.",
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