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 journalArticle

16 Citations (Scopus)

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

Fingerprint

Synucleins
Rats
Animals
Animal Models
Brain
Parkinson Disease
Dopamine
Mesencephalon
Pathology
Lewy Bodies
Corpus Striatum
Gliosis
Neurodegenerative diseases
Tyrosine 3-Monooxygenase
Neurites
Substantia Nigra
Basal Ganglia
Neurodegenerative Diseases
Brain Stem
Color

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Potential role of α-synuclein in neurodegeneration : Studies in a rat animal model. / Stoica, George; Lungu, Gina; Bjorklund, Nicole L.; Taglialatela, Giulio; Zhang, Xing; Chiu, Veronica; Hill, Herbert H.; Schenk, James O.; Murray, Ian.

In: Journal of Neurochemistry, Vol. 122, No. 4, 08.2012, p. 812-822.

Research output: Contribution to journalArticle

Stoica, G, Lungu, G, Bjorklund, NL, Taglialatela, G, Zhang, X, Chiu, V, Hill, HH, Schenk, JO & Murray, I 2012, 'Potential role of α-synuclein in neurodegeneration: Studies in a rat animal model', Journal of Neurochemistry, vol. 122, no. 4, pp. 812-822. https://doi.org/10.1111/j.1471-4159.2012.07805.x
Stoica, George ; Lungu, Gina ; Bjorklund, Nicole L. ; Taglialatela, Giulio ; Zhang, Xing ; Chiu, Veronica ; Hill, Herbert H. ; Schenk, James O. ; Murray, Ian. / Potential role of α-synuclein in neurodegeneration : Studies in a rat animal model. In: Journal of Neurochemistry. 2012 ; Vol. 122, No. 4. pp. 812-822.
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