Age-dependent synuclein pathology following traumatic brain injury in mice

K. Uryu, B. I. Giasson, L. Longhi, D. Martinez, I. Murray, V. Conte, M. Nakamura, K. Saatman, K. Talbot, T. Horiguchi, T. McIntosh, V. M Y Lee, J. Q. Trojanowski

Research output: Contribution to journalArticle

Abstract

Synucleins (Syn), a family of synaptic proteins, includes α-Syn, which plays a pivotal role in Parkinson's disease and related neurodegenerative diseases (synucleinopathies) by forming distinct brain pathologies (Lewy bodies and neurites). Since traumatic brain injury (TBI) is a poorly understood risk factor for Parkinson's disease, we examined the effects of TBI in the young and aged mouse brain on α-, β-, and γ-Syn. Immunohistochemical analysis showed that brains from sham-injured young and aged mice had normal α- and β-Syn immunoreactivity (IR) in neuropil of cortex, striatum, and hippocampus with little or no γ-Syn IR. At 1 week post TBI, the aged mouse brain showed a transient increase of α- and β-Syn IR in the neuropil as well as an induction of γ-Syn IR in subcortical axons. This was associated with strong labeling of striatal axon bundles by antibodies to altered or nitrated epitopes in α-Syn as well as by antibodies to inducible nitric oxide synthase. However, these TBI-induced changes disappeared by 16 weeks post TBI, and altered Syn IR was not seen in young mice subjected to TBI nor in α-Syn knockout mice while Western blots confirmed that TBI induced transient alterations of α-Syn in the mouse brains. This model of age-dependent TBI-induced transient alterations in α-Syn provides an opportunity to examine possible links between TBI and mechanisms of disease in synucleinopathies.

Original languageEnglish
Pages (from-to)214-224
Number of pages11
JournalExperimental Neurology
Volume184
Issue number1
DOIs
Publication statusPublished - Nov 2003

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Keywords

  • Mouse brain
  • Neurodegenerative disease
  • Synuclein
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Uryu, K., Giasson, B. I., Longhi, L., Martinez, D., Murray, I., Conte, V., Nakamura, M., Saatman, K., Talbot, K., Horiguchi, T., McIntosh, T., Lee, V. M. Y., & Trojanowski, J. Q. (2003). Age-dependent synuclein pathology following traumatic brain injury in mice. Experimental Neurology, 184(1), 214-224. https://doi.org/10.1016/S0014-4886(03)00245-0