Potential role of α-synuclein in neurodegeneration: studies in a rat animal model
Article first published online: 22 JUN 2012
© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry
Journal of Neurochemistry
Volume 122, Issue 4, pages 812–822, August 2012
How to Cite
Stoica, G., Lungu, G., Bjorklund, N. L., Taglialatela, G., Zhang, X., Chiu, V., Hill, H. H., Schenk, J. O. and Murray, I. (2012), Potential role of α-synuclein in neurodegeneration: studies in a rat animal model. Journal of Neurochemistry, 122: 812–822. doi: 10.1111/j.1471-4159.2012.07805.x
- Issue published online: 17 JUL 2012
- Article first published online: 22 JUN 2012
- Accepted manuscript online: 28 MAY 2012 08:35AM EST
- Received January 19, 2012; revised manuscript received May 14, 2012; accepted May 17, 2012.
- rat model
J. Neurochem. (2012) 122, 812–822.
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.