Reducing synuclein accumulation improves neuronal survival after spinal cord injury.
Exp Neurol
; 278: 105-15, 2016 Apr.
Article
in En
| MEDLINE
| ID: mdl-26854933
ABSTRACT
Spinal cord injury causes neuronal death, limiting subsequent regeneration and recovery. Thus, there is a need to develop strategies for improving neuronal survival after injury. Relative to our understanding of axon regeneration, comparatively little is known about the mechanisms that promote the survival of damaged neurons. To address this, we took advantage of lamprey giant reticulospinal neurons whose large size permits detailed examination of post-injury molecular responses at the level of individual, identified cells. We report here that spinal cord injury caused a select subset of giant reticulospinal neurons to accumulate synuclein, a synaptic vesicle-associated protein best known for its atypical aggregation and causal role in neurodegeneration in Parkinson's and other diseases. Post-injury synuclein accumulation took the form of punctate aggregates throughout the somata and occurred selectively in dying neurons, but not in those that survived. In contrast, another synaptic vesicle protein, synaptotagmin, did not accumulate in response to injury. We further show that the post-injury synuclein accumulation was greatly attenuated after single dose application of either the "molecular tweezer" inhibitor, CLR01, or a translation-blocking synuclein morpholino. Consequently, reduction of synuclein accumulation not only improved neuronal survival, but also increased the number of axons in the spinal cord proximal and distal to the lesion. This study is the first to reveal that reducing synuclein accumulation is a novel strategy for improving neuronal survival after spinal cord injury.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Spinal Cord Injuries
/
Gene Expression Regulation
/
Synucleins
/
Neurons
Limits:
Animals
Language:
En
Journal:
Exp Neurol
Year:
2016
Document type:
Article
Affiliation country:
United States