| First Author | Sauerbeck AD | Year | 2021 |
| Journal | Sci Rep | Volume | 11 |
| Issue | 1 | Pages | 11720 |
| PubMed ID | 34083630 | Mgi Jnum | J:313909 |
| Mgi Id | MGI:6720086 | Doi | 10.1038/s41598-021-91116-3 |
| Citation | Sauerbeck AD, et al. (2021) Alpha-synuclein increases in rodent and human spinal cord injury and promotes inflammation and tissue loss. Sci Rep 11(1):11720 |
| abstractText | Synucleinopathies are neurodegenerative diseases in which alpha-synuclein protein accumulates in neurons and glia. In these diseases, alpha-synuclein forms dense intracellular aggregates that are disease hallmarks and actively contribute to tissue pathology. Interestingly, many pathological mechanisms, including iron accumulation and lipid peroxidation, are shared between classical synucleinopathies such as Alzheimer's disease, Parkinson's disease and traumatic spinal cord injury (SCI). However, to date, no studies have determined if alpha-synuclein accumulation occurs after human SCI. To examine this, cross-sections from injured and non-injured human spinal cords were immunolabeled for alpha-synuclein. This showed robust alpha-synuclein accumulation in profiles resembling axons and astrocytes in tissue surrounding the injury, revealing that alpha-synuclein markedly aggregates in traumatically injured human spinal cords. We also detected significant iron deposition in the injury site, a known catalyst for alpha-synuclein aggregation. Next a rodent SCI model mimicking the histological features of human SCI revealed aggregates and structurally altered monomers of alpha-synuclein are present after SCI. To determine if alpha-synuclein exacerbates SCI pathology, alpha-synuclein knockout mice were tested. Compared to wild type mice, alpha-synuclein knockout mice had significantly more spared axons and neurons and lower pro-inflammatory mediators, macrophage accumulation, and iron deposition in the injured spinal cord. Interestingly, locomotor analysis revealed that alpha-synuclein may be essential for dopamine-mediated hindlimb function after SCI. Collectively, the marked upregulation and long-lasting accumulation of alpha-synuclein and iron suggests that SCI may fit within the family of synucleinopathies and offer new therapeutic targets for promoting neuron preservation and improving function after spinal trauma. |
