Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human α-synuclein

Merja Lakso, Suvi Vartiainen, Anu Maarit Moilanen, Jouni Sirviö, James H. Thomas, Richard Nass, Randy D. Blakely, Garry Wong

Research output: Contribution to journalArticle

242 Citations (Scopus)

Abstract

Overexpression of human α-synuclein in model systems, including cultured neurons, drosophila and mice, leads to biochemical and pathological changes that mimic synucleopathies including Parkinson's disease. We have overexpressed both wild-type (WT) and mutant alanine53 → threonine (A53T) human α-synuclein by transgenic injection into Caenorhabditis elegans. Motor deficits were observed when either WT or A53T α-synuclein was overexpressed with a pan-neuronal or motor neuron promoter. Neuronal and dendritic loss were accelerated in all three sets of C. elegans dopaminergic neurons when human α-synuclein was overexpressed under the control of a dopaminergic neuron or pan-neuronal promoter, but not with a motor neuron promoter. There were no significant differences in neuronal loss between overexpressed WT and A53T forms or between worms of different ages (4 days, 10 days or 2 weeks). These results demonstrate neuronal and behavioral perturbations elicited by human α-synuclein in C. elegans that are dependent upon expression in specific neuron subtypes. This transgenic model in C. elegans, an invertebrate organism with excellent experimental resources for further genetic manipulation, may help facilitate dissection of pathophysiologic mechanisms of various synucleopathies.

Original languageEnglish (US)
Pages (from-to)165-172
Number of pages8
JournalJournal of Neurochemistry
Volume86
Issue number1
DOIs
StatePublished - Jul 2003
Externally publishedYes

Fingerprint

Synucleins
Caenorhabditis elegans
Neurons
Threonine
Dopaminergic Neurons
Motor Neurons
Dissection
Invertebrates
Drosophila
Parkinson Disease
Injections

Keywords

  • α-synuclein
  • Model organism
  • Motor neuron
  • Neurodegeneration
  • Worm transgenic

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human α-synuclein. / Lakso, Merja; Vartiainen, Suvi; Moilanen, Anu Maarit; Sirviö, Jouni; Thomas, James H.; Nass, Richard; Blakely, Randy D.; Wong, Garry.

In: Journal of Neurochemistry, Vol. 86, No. 1, 07.2003, p. 165-172.

Research output: Contribution to journalArticle

Lakso, M, Vartiainen, S, Moilanen, AM, Sirviö, J, Thomas, JH, Nass, R, Blakely, RD & Wong, G 2003, 'Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human α-synuclein', Journal of Neurochemistry, vol. 86, no. 1, pp. 165-172. https://doi.org/10.1046/j.1471-4159.2003.01809.x
Lakso, Merja ; Vartiainen, Suvi ; Moilanen, Anu Maarit ; Sirviö, Jouni ; Thomas, James H. ; Nass, Richard ; Blakely, Randy D. ; Wong, Garry. / Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human α-synuclein. In: Journal of Neurochemistry. 2003 ; Vol. 86, No. 1. pp. 165-172.
@article{fab058e176f24b3fabbc01e6c25fbf9d,
title = "Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human α-synuclein",
abstract = "Overexpression of human α-synuclein in model systems, including cultured neurons, drosophila and mice, leads to biochemical and pathological changes that mimic synucleopathies including Parkinson's disease. We have overexpressed both wild-type (WT) and mutant alanine53 → threonine (A53T) human α-synuclein by transgenic injection into Caenorhabditis elegans. Motor deficits were observed when either WT or A53T α-synuclein was overexpressed with a pan-neuronal or motor neuron promoter. Neuronal and dendritic loss were accelerated in all three sets of C. elegans dopaminergic neurons when human α-synuclein was overexpressed under the control of a dopaminergic neuron or pan-neuronal promoter, but not with a motor neuron promoter. There were no significant differences in neuronal loss between overexpressed WT and A53T forms or between worms of different ages (4 days, 10 days or 2 weeks). These results demonstrate neuronal and behavioral perturbations elicited by human α-synuclein in C. elegans that are dependent upon expression in specific neuron subtypes. This transgenic model in C. elegans, an invertebrate organism with excellent experimental resources for further genetic manipulation, may help facilitate dissection of pathophysiologic mechanisms of various synucleopathies.",
keywords = "α-synuclein, Model organism, Motor neuron, Neurodegeneration, Worm transgenic",
author = "Merja Lakso and Suvi Vartiainen and Moilanen, {Anu Maarit} and Jouni Sirvi{\"o} and Thomas, {James H.} and Richard Nass and Blakely, {Randy D.} and Garry Wong",
year = "2003",
month = "7",
doi = "10.1046/j.1471-4159.2003.01809.x",
language = "English (US)",
volume = "86",
pages = "165--172",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human α-synuclein

AU - Lakso, Merja

AU - Vartiainen, Suvi

AU - Moilanen, Anu Maarit

AU - Sirviö, Jouni

AU - Thomas, James H.

AU - Nass, Richard

AU - Blakely, Randy D.

AU - Wong, Garry

PY - 2003/7

Y1 - 2003/7

N2 - Overexpression of human α-synuclein in model systems, including cultured neurons, drosophila and mice, leads to biochemical and pathological changes that mimic synucleopathies including Parkinson's disease. We have overexpressed both wild-type (WT) and mutant alanine53 → threonine (A53T) human α-synuclein by transgenic injection into Caenorhabditis elegans. Motor deficits were observed when either WT or A53T α-synuclein was overexpressed with a pan-neuronal or motor neuron promoter. Neuronal and dendritic loss were accelerated in all three sets of C. elegans dopaminergic neurons when human α-synuclein was overexpressed under the control of a dopaminergic neuron or pan-neuronal promoter, but not with a motor neuron promoter. There were no significant differences in neuronal loss between overexpressed WT and A53T forms or between worms of different ages (4 days, 10 days or 2 weeks). These results demonstrate neuronal and behavioral perturbations elicited by human α-synuclein in C. elegans that are dependent upon expression in specific neuron subtypes. This transgenic model in C. elegans, an invertebrate organism with excellent experimental resources for further genetic manipulation, may help facilitate dissection of pathophysiologic mechanisms of various synucleopathies.

AB - Overexpression of human α-synuclein in model systems, including cultured neurons, drosophila and mice, leads to biochemical and pathological changes that mimic synucleopathies including Parkinson's disease. We have overexpressed both wild-type (WT) and mutant alanine53 → threonine (A53T) human α-synuclein by transgenic injection into Caenorhabditis elegans. Motor deficits were observed when either WT or A53T α-synuclein was overexpressed with a pan-neuronal or motor neuron promoter. Neuronal and dendritic loss were accelerated in all three sets of C. elegans dopaminergic neurons when human α-synuclein was overexpressed under the control of a dopaminergic neuron or pan-neuronal promoter, but not with a motor neuron promoter. There were no significant differences in neuronal loss between overexpressed WT and A53T forms or between worms of different ages (4 days, 10 days or 2 weeks). These results demonstrate neuronal and behavioral perturbations elicited by human α-synuclein in C. elegans that are dependent upon expression in specific neuron subtypes. This transgenic model in C. elegans, an invertebrate organism with excellent experimental resources for further genetic manipulation, may help facilitate dissection of pathophysiologic mechanisms of various synucleopathies.

KW - α-synuclein

KW - Model organism

KW - Motor neuron

KW - Neurodegeneration

KW - Worm transgenic

UR - http://www.scopus.com/inward/record.url?scp=0037971209&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037971209&partnerID=8YFLogxK

U2 - 10.1046/j.1471-4159.2003.01809.x

DO - 10.1046/j.1471-4159.2003.01809.x

M3 - Article

VL - 86

SP - 165

EP - 172

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 1

ER -