title: Synuclein accumulation is associated with cell-specific neuronal death after spinal cord injury.
abstract: Spinal cord injury axotomizes neurons and induces many of them to die, whereas others survive. Therefore, it is important to identify factors that lead to neuronal death after injury as a first step toward developing better strategies for increasing neuronal survival and functional recovery. However, the intrinsic molecular pathways that govern whether an injured neuron lives or dies remain surprisingly unclear. To address this question, we took advantage of the large size of giant reticulospinal (RS) neurons in the brain of the lamprey, Petromyzon marinus. We report that axotomy of giant RS neurons induces a select subset of them to accumulate high levels of synuclein, a synaptic vesicle-associated protein whose abnormal accumulation is linked to Parkinson's disease. Injury-induced synuclein accumulation occurred only in neurons that were classified as "poor survivors" by both histological and Fluoro-Jade C staining. In contrast, post-injury synuclein immunofluorescence remained at control levels in neurons that were identified as "good survivors." Synuclein accumulation appeared in the form of aggregated intracellular inclusions. Cells that accumulated synuclein also exhibited more ubiquitin-containing inclusions, similar to what occurs during disease states. When synuclein levels and cell vitality were measured in the same neurons, it became clear that synuclein accumulation preceded and strongly correlated with subsequent neuronal death. Thus, synuclein accumulation is identified as a marker and potential risk factor for forthcoming neuronal death after axotomy, expanding its implications beyond the neurodegenerative diseases.
authors: Section of Molecular Cell and Developmental Biology, Institute for Cell and Molecular Biology, Institute for Neuroscience, University of Texas at Austin, Austin, Texas 78712, USA.
authors: David J
authors: DJ
authors: Busch
authors: Jennifer R
authors: JR
authors: Morgan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D016923:Cell Death / Q000502:physiology; D005455:Fluorescent Antibody Technique; D017403:In Situ Hybridization; D002479:Inclusion Bodies / Q000737:chemistry / Q000378:metabolism; D007798:Lampreys; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology*; D051843:Synucleins / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051843:Synucleins; D025801:Ubiquitin