Cited by 502Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNeuroinflammation and Neurodegeneration Mechanisms

Differential neuropathological alterations in transgenic mice expressing α‐synuclein from the platelet‐derived growth factor and Thy‐1 promoters

Rockenstein, Edward, Mallory, Margaret, Hashimoto, Makoto, Song, David, Shults, Clifford W., Lang, Ingrid, Masliah, Eliezer·2002·Journal of Neuroscience Research

Abstract

Accumulation of alpha-synuclein has been associated with neurodegenerative disorders, such as Lewy body disease and multiple system atrophy. We previously showed that expression of wild-type human alpha-synuclein in transgenic mice results in motor and dopaminergic deficits associated with inclusion formation. To determine whether different levels of human alpha-synuclein expression from distinct promoters might result in neuropathology mimicking other synucleopathies, we compared patterns of human alpha-synuclein accumulation in the brains of transgenic mice expressing this molecule from the murine Thy-1 and platelet-derived growth factor (PDGF) promoters. In murine Thy-1-human alpha-synuclein transgenic mice, this protein accumulated in synapses and neurons throughout the brain, including the thalamus, basal ganglia, substantia nigra, and brainstem. Expression of human alpha-synuclein from the PDGF promoter resulted in accumulation in synapses of the neocortex, limbic system, and olfactory regions as well as formation of inclusion bodies in neurons in deeper layers of the neocortex. Furthermore, one of the intermediate expressor lines (line M) displayed human alpha-synuclein expression in glial cells mimicking some features of multiple system atrophy. These results show a more widespread accumulation of human alpha-synuclein in transgenic mouse brains. Taken together, these studies support the contention that human alpha-synuclein expression in transgenic mice might mimic some neuropathological alterations observed in Lewy body disease and other synucleopathies, such as multiple system atrophy.

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Crossref · 10.1002/jnr.10231

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Authors
Rockenstein, E., Mallory, M., Hashimoto, M., Song, D., Shults, C. W., Lang, I., & Masliah, E.
Affiliations
  • University of California San Diego (US)
  • University of Graz (AT)
Corresponding author
Masliah, Eliezer
Venue
Journal of Neuroscience Research
Publisher
Wiley
Published
2002-05-23
Volume
68
Issue
5
Pages
568-578
ISSN
  • 0360-4012 (ISSN-L)
  • 1097-4547
OpenAlex
W2080949995
Cited by
502
References
46
Citations by year
2026: 17 · 2025: 24 · 2024: 19 · 2023: 23 · 2022: 32 · 2021: 31 · 2020: 26 · 2019: 17 · 2018: 31 · 2017: 28 · 2016: 16 · 2015: 22 · 2014: 39 · 2013: 20 · 2012: 32
FWCI
5.09
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neuroscience Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r29ag010869-05)
  • National Institute on Aging (P50AG005131, AG-5131, AG 18440, AG10869)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
alpha-synuclein, transgenic mice, Lewy body disease, multiple system atrophy, glial cells, dopaminergic deficit, Lewy bodies, neocortex, substantia nigra, basal ganglia, thalamus, brainstem, motor impairment
MeSH terms
Animals, Humans, Limbic System, Mice, Transgenic, Nerve Tissue Proteins, Neuroglia, Neurons, Platelet-Derived Growth Factor, Promoter Regions, Genetic, Substantia Nigra, Gene Expression, Thy-1 Antigens, Multiple System Atrophy, Neocortex, Lewy Body Disease, Mice, Synucleins, alpha-Synuclein

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