151. Age-dependent synuclein pathology following traumatic brain injury in mice
- Author
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Kathryn E. Saatman, Michio Nakamura, Valeria Conte, Ian V.J. Murray, Benoit I. Giasson, Virginia M.-Y. Lee, Konrad Talbot, T Horiguchi, Kunihiro Uryu, Daniel Martinez, Luca Longhi, John Q. Trojanowski, and Tracy K. McIntosh
- Subjects
Pathology ,medicine.medical_specialty ,Aging ,Traumatic brain injury ,animal diseases ,Central nervous system ,Blotting, Western ,Molecular Conformation ,Synucleins ,Hippocampus ,Nerve Tissue Proteins ,Biology ,Epitopes ,Mice ,Developmental Neuroscience ,Isomerism ,medicine ,Neuropil ,Animals ,heterocyclic compounds ,Synucleinopathies ,Cerebral Cortex ,Mice, Knockout ,Lewy body ,Brain ,Parkinson Disease ,medicine.disease ,Immunohistochemistry ,Axons ,nervous system diseases ,medicine.anatomical_structure ,nervous system ,Neurology ,Brain Injuries ,Knockout mouse ,health occupations ,Synuclein - Abstract
Synucleins (Syn), a family of synaptic proteins, includes alpha-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 alpha-, beta-, and gamma-Syn. Immunohistochemical analysis showed that brains from sham-injured young and aged mice had normal alpha- and beta-Syn immunoreactivity (IR) in neuropil of cortex, striatum, and hippocampus with little or no gamma-Syn IR. At 1 week post TBI, the aged mouse brain showed a transient increase of alpha- and beta-Syn IR in the neuropil as well as an induction of gamma-Syn IR in subcortical axons. This was associated with strong labeling of striatal axon bundles by antibodies to altered or nitrated epitopes in alpha-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 alpha-Syn knockout mice while Western blots confirmed that TBI induced transient alterations of alpha-Syn in the mouse brains. This model of age-dependent TBI-induced transient alterations in alpha-Syn provides an opportunity to examine possible links between TBI and mechanisms of disease in synucleinopathies.
- Published
- 2003