Cited by 53Parkinson's Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsTelomeres, Telomerase, and Senescence

Telomere shortening leads to an acceleration of synucleinopathy and impaired microglia response in a genetic mouse model

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Scheffold, Annika, Holtman, Inge R., Dieni, Sandra, Brouwer, Nieske, Katz, Sarah-Fee, Jebaraj, Billy Michael Chelliah, Kahle, Philipp J., Hengerer, Bastian +6 more·2016·Acta Neuropathologica Communications

Abstract

Parkinson's disease is one of the most common neurodegenerative disorders of the elderly and ageing hence described to be a major risk factor. Telomere shortening as a result of the inability to fully replicate the ends of linear chromosomes is one of the hallmarks of ageing. The role of telomere dysfunction in neurological diseases and the ageing brain is not clarified and there is an ongoing discussion whether telomere shortening is linked to Parkinson's disease. Here we studied a mouse model of Parkinson's disease (Thy-1 [A30P] α-synuclein transgenic mouse model) in the background of telomere shortening (Terc knockout mouse model). α-synuclein transgenic mice with short telomeres (αSYN(tg/tg) G3Terc(-/-)) developed an accelerated disease with significantly decreased survival. This accelerated phenotype of mice with short telomeres was characterized by a declined motor performance and an increased formation of α-synuclein aggregates. Immunohistochemical analysis and mRNA expression studies revealed that the disease end-stage brain stem microglia showed an impaired response in αSYN(tg/tg) G3Terc(-/-) microglia animals. These results provide the first experimental data that telomere shortening accelerates α-synuclein pathology that is linked to limited microglia function in the brainstem.

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  • Mice carrying a homozygous germline deletion of the telomerase RNA component gene (Terc−/−) exhibit critically short telomeres and premature development of age-related pathologies from the second or third generation.

    “In particular, mice carrying a homozygous germline deletion of the telomerase RNA component gene (Terc−/−) exhibit critically short telomeres and a premature development of age-related pathologies from the second or third generation [8, 18–20, 51, 70, 72, 101, 103]”

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  1. [15]Tremblay ME Lowery RL Majewska AK Microglial interactions with synapses are modulated by visual experience PLoS Biol 2011 8 e1000527 10.1371/journal.pbio.1000527 21072242 PMC2970556 · DOI · Paper page

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Authors
Scheffold, A., Holtman, I. R., Dieni, S., Brouwer, N., Katz, S.-F., Jebaraj, B. M. C., Kahle, P. J., Hengerer, B., Lechel, A., Stilgenbauer, S., Boddeke, E. W. G. M., Eggen, B. J. L., Rudolph, K.-L., & Biber, K.
Affiliations
  • Universität Ulm (DE)
  • University Medical Center Groningen (NL)
  • University Medical Center Freiburg (DE)
  • Hertie Institute for Clinical Brain Research (DE)
  • Boehringer Ingelheim (Germany) (DE)
  • Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
Corresponding author
Biber, Knut
Venue
Acta Neuropathologica Communications
Published
2016-08-22
Volume
4
Issue
1
Pages
87-87
ISSN
2051-5960 (ISSN-L)
OpenAlex
W2517605453
Cited by
53
References
89
Citations by year
2026: 4 · 2025: 4 · 2024: 7 · 2023: 6 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 3 · 2018: 3 · 2017: 7
FWCI
3.26
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Acta Neuropathologica Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
  • Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
Funders
Deutsche Forschungsgemeinschaft (BI 668/2-2 and BI 668/5-1)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Keywords
telomere shortening, Parkinson's disease, alpha-synuclein, synucleinopathies, microglia, microglial activation, alpha-synuclein aggregates, brainstem, motor performance, aging, neurodegeneration
MeSH terms
Animals, Brain Stem, Postural Balance, Humans, Mice, Inbred C57BL, Mice, Transgenic, Motor Activity, Phenotype, RNA, Messenger, Time Factors, Microglia, Disease Progression, Parkinsonian Disorders, alpha-Synuclein, Telomere Shortening, Protein Aggregation, Pathological

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