Reducing synuclein accumulation improves neuronal survival after spinal cord injury
| Autor: | Alexandra J. van Brummen, Scott R. Allen, Susan M. L. Banks, Thomas Schrader, Frank-Gerrit Klärner, Stephanie M. Fogerson, Jennifer R. Morgan, Robin Roychaudhuri, David J. Busch, Gal Bitan |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Morpholino Parkinson's disease Cell Count Neurodegenerative Regenerative Medicine Morpholinos 0302 clinical medicine 2.1 Biological and endogenous factors Psychology Axon Aetiology Spinal Cord Injury Spinal cord injury Neurons CLR01 Lamprey Neurodegeneration Lampreys Organophosphates medicine.anatomical_structure Neurology Larva Neurological Bridged-Ring Compounds Physical Injury - Accidents and Adverse Effects 1.1 Normal biological development and functioning Clinical Sciences Chemie Synucleins Biology Synaptic vesicle Article Synaptotagmin 1 03 medical and health sciences Developmental Neuroscience Underpinning research medicine Animals Traumatic Head and Spine Injury Spinal Cord Injuries Analysis of Variance Neurology & Neurosurgery Animal Neurosciences Spinal cord medicine.disease Synaptotagmin Molecular tweezer Disease Models Animal 030104 developmental biology nervous system Gene Expression Regulation Disease Models Synuclein Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Experimental neurology, vol 278 Fogerson, SM; van Brummen, AJ; Busch, DJ; Allen, SR; Roychaudhuri, R; Banks, SML; et al.(2016). Reducing synuclein accumulation improves neuronal survival after spinal cord injury. EXPERIMENTAL NEUROLOGY, 278, 105-115. doi: 10.1016/j.expneurol.2016.02.004. UCLA: Retrieved from: http://www.escholarship.org/uc/item/5hm3r4j3 |
| DOI: | 10.1016/j.expneurol.2016.02.004. |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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