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Role of synucleins in traumatic brain injury -- an experimental in vitro and in vivo study in mice

Surgucheva, Irina, He, Shuangteng, Rich, Megan C., Sharma, Ram, Ninkina, Natalia, Stahel, Philip F. and Surguchov, Andrei 2014. Role of synucleins in traumatic brain injury -- an experimental in vitro and in vivo study in mice. Molecular and Cellular Neuroscience 63 , pp. 114-123. 10.1016/j.mcn.2014.10.005

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Abstract

Synucleins are small prone to aggregate proteins associated with several neurodegenerative diseases (NDDs), however their role in traumatic brain injury (TBI) is an emerging area of investigation. Using in vitro scratch injury model and in vivo mouse weight-drop model we have found that the injury causes alterations in the expression and localization of synucleins near the damaged area. Before injury, α-synuclein is diffused in the cytoplasm of neurons and γ-synuclein is both in the cytoplasm and nucleus of oligodendrocytes. After the scratch injury of the mixed neuronal and glial culture, α-synuclein forms punctate structures in the cytoplasm of neurons and γ-synuclein is almost completely localized to the nucleus of the oligodendrocytes. Furthermore, the amount of post-translationally modified Met38-oxidized γ-synuclein is increased 3.8 fold 24 h after the scratch. α- and γ-synuclein containing cells increased in the initially cell free scratch zone up to 24 h after the scratch. Intracellular expression and localization of synucleins are also changed in a mouse model of focal closed head injury, using a standardized weight drop device. γ-Synuclein goes from diffuse to punctate staining in a piriform cortex near the amygdala, which may reflect the first steps in the formation of deposits/inclusions. Surprisingly, oxidized γ-synuclein co-localizes with cofilin-actin rods in the thalamus, which are absent in all other regions of the brain. These structures reach their peak amounts 7 days after injury. The changes in γ-synuclein localization are accompanied by injury-induced alterations in the morphology of both astrocytes and neurons.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Biosciences
Subjects: Q Science > Q Science (General)
Publisher: Elsevier
ISSN: 1044-7431
Date of Acceptance: 23 October 2014
Last Modified: 20 Feb 2019 16:57
URI: http://orca.cf.ac.uk/id/eprint/68642

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