Age-dependent synuclein pathology following traumatic brain injury in mice.
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.
Uryu
K
K
The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Giasson
B I
BI
Longhi
L
L
Martinez
D
D
Murray
I
I
Conte
V
V
Nakamura
M
M
Saatman
K
K
Talbot
K
K
Horiguchi
T
T
McIntosh
T
T
Lee
V M-Y
VM
Trojanowski
J Q
JQ
D000375:Aging / Q000473:pathology*; D000818:Animals; D001369:Axons / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000473:pathology*; D001930:Brain Injuries / Q000473:pathology*; D002540:Cerebral Cortex / Q000293:injuries / Q000473:pathology; D000939:Epitopes / Q000235:genetics; D007150:Immunohistochemistry; D007536:Isomerism; D051379:Mice; D018345:Mice, Knockout; D008968:Molecular Conformation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D051843:Synucleins
D000939:Epitopes; D009419:Nerve Tissue Proteins; D051843:Synucleins