Over-expression of alpha-synuclein in the nervous system enhances axonal degeneration after peripheral nerve lesion in a transgenic mouse strain

Authors: Siebert, Heike; Kahle, Philipp J.; Kramer, Michael L.¹; Isik, Thomas¹; Schlüter, Oliver M.²; Schulz-Schaeffer, Walter J.¹; Brück, Wolfgang¹

Source: Journal of Neurochemistry, Volume 114, Number 4, August 2010 , pp. 1007-1018(12)

Publisher: Wiley-Blackwell

Abstract:

J. Neurochem. (2010) 114, 1007-1018. Abstract

Wallerian degeneration in peripheral nerves occurs after a traumatic insult when the distal nerve part degenerates while peripheral macrophages enter the nerve stump and remove the accruing debris by phagozytosis. We used an experimental model to investigate the effect of either the absence or over-expression of α-synuclein (α-syn) after transecting the sciatic nerves of mice. α-Synuclein is a major component of Lewy bodies and its aggregation results in a premature destruction of nerve cells. It has also been found present in different peripheral nerves but its role in the axon remains still unclear. Following sciatic nerve transection in different mouse strains, we investigated the numbers of invading macrophages, the amounts of remaining myelin and axons 6 days after injury. All mice showed clear signs of Wallerian degeneration, but transgenic mice expressing human wild-type α-syn showed lower numbers of invading macrophages, less preserved myelin and significantly lower numbers of preserved axons in comparison with either knockout mice or a mouse strain with a spontaneous deletion of α-syn. The use of protein aggregation filtration blots and paraffin-embedded tissue blots displayed depositions of α-syn aggregates within sciatic nerve axons of transgenic mice. Thicker myelin sheaths and higher numbers of mitochondria were detected in old α-syn transgenic mice. In a human sural nerve, α-syn could also be identified within axons. Thus, α-syn and its aggregates are not only a component of Lewy bodies and synapses but also of axons and these aggregates might interfere with axonal transport. α-Synuclein transgenic mice represent an appropriate model for investigations on axonal transport in neurodegenerative diseases.

Keywords: knockout mice; myelin; paraffin-embedded tissue blot; protein aggregation filtration blot; sciatic nerve; Wallerian degeneration

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1471-4159.2010.06832.x

Affiliations: 1: Institute of Neuropathology, University Medical Centre Goettingen, Goettingen, Germany 2: Department Molecular Neurobiology, European Neuroscience Institute Goettingen, Goettingen, Germany

Publication date: 2010-08-01

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