Potential role of α-synuclein in neurodegeneration: Studies in a rat animal model

George Stoica, Gina Lungu, Nicole L. Bjorklund, Giulio Taglialatela, Xing Zhang, Veronica Chiu, Herbert H. Hill, James O. Schenk, Ian Murray

    Research output: Contribution to journalArticlepeer-review

    23 Scopus citations

    Abstract

    Neuronal protein α-synuclein (α-syn) is an essential player in the development of neurodegenerative diseases called synucleinopathies. A spontaneous autosomal recessive rat model for neurodegeneration was developed in our laboratory. These rats demonstrate progressive increases in α-syn in the brain mesencephalon followed by loss of dopaminergic terminals in the basal ganglia (BG) and motor impairments. The severity of pathology is directly related to the overexpression of α-syn and parallel decrease in dopamine (DA) level in the striatum (ST) of affected rats. The neurodegeneration in this model is characterized by the presence of perikarya and neurites Lewis bodies (LB) and diffuse marked accumulation of perikaryal α-syn in the substantia nigra (SN), brain stem (BS), and striatum (ST) along with neuronal loss. Light and ultrastructural analyses revealed that the process of neuronal degeneration is a 'dying back' type. The disease process is accompanied by gliosis and release of inflammatory cytokines. This neurodegeneration is a multisystemic disease and implicate α-syn as a major factor in the pathogenesis of this inherited autosomal recessive animal model. Decrease dopamine (DA) and overexpression of α-syn in the brain mesencephalon may provide a naturally occurring animal model for Parkinson's disease (PD) and other synucleinopathies that reproduces significant pathological, neurochemical, and behavioral features of the human disease. A novel rat model for Parkinson?s diseaseThis study was motivated by the lack of animal models that reproduce key neuropathological features of Parkinson's disease. Affected rats show increased levels of brain α-synuclein, loss of striatal dopamine and tyrosine hydroxylase (TH), Lewy body pathology and locomotor behavior. This inherited autosomal recessive disorder provide a naturally occurring animal model for Parkinson's disease and other synucleinopathies. The affected BD-IV rats can be identified by the gray color of their coat.

    Original languageEnglish (US)
    Pages (from-to)812-822
    Number of pages11
    JournalJournal of neurochemistry
    Volume122
    Issue number4
    DOIs
    StatePublished - Aug 2012

    Keywords

    • Parkinson's
    • dopamine
    • neurodegeneration
    • rat model
    • α-synuclein

    ASJC Scopus subject areas

    • Biochemistry
    • Cellular and Molecular Neuroscience

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