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Title: Neuropathology and neurodegeneration in rodent brain induced by lentiviral vector-mediated overexpression of alpha-synuclein
Authors: Lauwers, Erwin
Debyser, Zeger
Van Dorpe, Jo
De Strooper, Bart
Nuttin, Bart
Baekelandt, Veerle # ×
Issue Date: Aug-2003
Publisher: International Society of Neuropathology
Series Title: Brain Pathology vol:13 issue:3 pages:364-372
Abstract: Two mutations in alpha-synuclein, the main constituent of Lewy bodies, have been identified in familial Parkinson's disease. We have stereotactically injected lentiviral vectors encoding wild-type and A30P mutant human alpha-synuclein in different brain regions (striatum, substantia nigra, amygdala) of mice. Overexpression of alpha-synuclein induced time-dependent neuropathological changes reminiscent of Lewy pathology: abnormal accumulation of alpha-synuclein in cell bodies and neurites, alpha-synuclein-positive neuritic varicosities and cytoplasmic inclusions that stained with ubiquitin antibodies and became larger and more frequent with time. After one year, alpha-synuclein- and ubiquitin-positive neurons displayed a degenerative morphology and a significant loss of alpha-synuclein-positive cells was observed. Similar findings were observed with both the wild-type and the A30P mutant form of alpha-synuclein and this in different brain regions. This indicates that overexpression of alpha-synuclein is sufficient to induce Lewy-like pathology and neurodegeneration and that this effect is not restricted to dopaminergic cells. Our data also demonstrate the use of lentiviral vectors to create animal models for neurodegenerative diseases.
ISSN: 1015-6305
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Virology and Gene Therapy
Animal Physiology and Neurobiology Section - miscellaneous
Research Group Experimental Neurosurgery and Neuroanatomy
Research Group for Neurobiology and Gene Therapy
Molecular Genetics Section (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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