Prion-like transmission of α-synuclein pathology in the context of an NFL null background. (20th November 2017)

• Record Type: Journal Article
• Authors: Rutherford, Nicola J.; Brooks, Mieu; Riffe, Cara J.; Gorion, Kimberly-Marie M.; Howard, Jasie K.; Dhillon, Jess-Karan S.; Giasson, Benoit I.
• Is Part Of: Neuroscience letters. Volume 661(2017)
• Page Start: 114
• Page End: 120
• Publication Date: 2017-11-20
• Subjects: Aβ amyloid β -- AD Alzheimer's disease -- ALS amyotrophic lateral sclerosis -- αS α-synuclein -- BCA bicinchoninic acid -- BSA bovine serum albumin -- CMT Charcot Marie Tooth -- DAB 3, 3′ diaminobenzidine -- E. coli Escherichia coli -- FBS fetal bovine serum -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- K114 (trans, trans)-1-bromo-2, 5-bis-(4-hydroxy)styrylbenzene -- M83 A53T human αS transgenic mice -- NEFH heavy molecular mass neurofilament subunit gene -- NEFL low molecular mass neurofilament subunit gene -- NF neurofilament -- NFH heavy molecular mass neurofilament subunit -- NFID neurofilament inclusion disease -- NFL low molecular mass neurofilament subunit -- NFM medium molecular mass neurofilament subunit -- NFT neurofibrillary tangle -- PBS phosphate buffered saline -- PCR polymerase chain reaction -- PD Parkinson's disease -- pSer129 phosphorylated serine 129 -- SDS sodium dodecyl sulfate -- SNCA α-synuclein gene -- T44 human tau transgenic mice -- TBS Tris buffered saline; Neurofilaments -- α-Synuclein -- NFL gene (NEFL) knockout -- Parkinson's disease -- Transgenic mice -- Synucleinopathy; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2017.09.054
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Seeding of αS pathology in A53T human αS transgenic mice on an NFL null background. Cerebral prion-like transmission of αS is maintained in an NFL null environment. Paucity of neurofilaments does not influence peripheral to CNS transmission of αS. Abstract: Neurofilaments are a major component of the axonal cytoskeleton in neurons and have been implicated in a number of neurodegenerative diseases due to their presence within characteristic pathological inclusions. Their contributions to these diseases are not yet fully understood, but previous studies investigated the effects of ablating the obligate subunit of neurofilaments, low molecular mass neurofilament subunit (NFL), on disease phenotypes in transgenic mouse models of Alzheimer's disease and tauopathy. Here, we tested the effects of ablating NFL in α-synuclein M83 transgenic mice expressing the human pathogenic A53T mutation, by breeding them onto an NFL null background. The induction and spread of α-synuclein inclusion pathology was triggered by the injection of preformed α-synuclein fibrils into the gastrocnemius muscle or hippocampus in M83 versus M83/NFL null mice. We observed no difference in the post-injection time to motor-impairment and paralysis endpoint or amount and distribution of α-synuclein inclusion pathology in the muscle injected M83 and M83/NFL null mice. Hippocampal injected M83/NFL null mice displayed subtle region-specific differences in the amount of α-synuclein inclusions however, pathology was observed in the same regions as the M83 mice. Overall, we observed only minor differences in the induction and transmission of α-synuclein pathology in these induced models of synucleinopathy in the presence or absence of NFL. This suggests that NFL and neurofilaments do not play a major role in influencing the induction and transmission of α-synuclein aggregation.