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Differential neuropathological alterations in transgenic mice expressing alpha-synuclein from the platelet-derived growth factor and Thy-1 promoters
Rockenstein E, Mallory M, Hashimoto M, Song D, Shults CW, Lang I, Masliah E.. Journal of neuroscience research, 2002-06-01
Topic: Brain proteins, microglia and lab models
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.
Key findings
- 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.
- 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.
Why it matters
In transgenic mice, expressing human alpha-synuclein from different promoters led to different patterns of alpha-synuclein accumulation, including inclusion bodies in some neurons. This is an animal model study of synuclein pathology, not a treatment or cure.
Study details
- Evidence strengthLow
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neuroscience research) |
| Journal's citation record | 2 / 4 | Journal of Neuroscience Research: journal h-index 222 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2002 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “transgenic”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 501 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 19.3 citations a year over 26 year(s) since 2002 |
| Impact for its field and year | 3 / 6 | Cited 4.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 other studies in this library |
| Still being cited | 3 / 4 | Cited 59 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Eliezer Masliah: h-index 195 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California San Diego: institution h-index 1,852 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12111846) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Rockenstein, E., Mallory, M., Hashimoto, M., Song, D., Shults, C. W., Lang, I., et al. (2002). Differential neuropathological alterations in transgenic mice expressing alpha-synuclein from the platelet-derived growth factor and Thy-1 promoters. Journal of neuroscience research. https://doi.org/10.1002/jnr.10231
Vancouver
Rockenstein E, Mallory M, Hashimoto M, Song D, Shults CW, Lang I, et al. Differential neuropathological alterations in transgenic mice expressing alpha-synuclein from the platelet-derived growth factor and Thy-1 promoters. Journal of neuroscience research. 2002. doi:10.1002/jnr.10231. PMID: 12111846.
BibTeX
@article{rockenstein2002-12111846,
author = {Rockenstein, E. and Mallory, M. and Hashimoto, M. and Song, D. and Shults, C. W. and Lang, I. and Masliah, E.},
title = {{Differential neuropathological alterations in transgenic mice expressing alpha-synuclein from the platelet-derived growth factor and Thy-1 promoters}},
journal = {Journal of neuroscience research},
year = {2002},
doi = {10.1002/jnr.10231},
pmid = {12111846},
url = {https://doi.org/10.1002/jnr.10231}
}
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