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Cited by 43Down syndrome and intellectual disability researchTea Polyphenols and EffectsAlzheimer's disease research and treatments

Evaluation of the therapeutic potential of Epigallocatechin-3-gallate (EGCG) via oral gavage in young adult down syndrome mice

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Goodlett, Charles R., Stringer, Megan, LaCombe, Jonathan, Patel, Roshni, Wallace, Joseph M., Roper, Randall J.·2020·Scientific Reports
DOI 10.1038/s41598-020-67133-zPMC PMC7319987
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Abstract

Epigallocatechin-3-gallate (EGCG) is a candidate therapeutic for Down syndrome (DS) phenotypes based on in vitro inhibition of DYRK1A, a triplicated gene product of Trisomy 21 (Ts21). Consumption of green tea extracts containing EGCG improved some cognitive and behavioral outcomes in DS mouse models and in humans with Ts21. In contrast, treatment with pure EGCG in DS mouse models did not improve neurobehavioral phenotypes. This study tested the hypothesis that 200 mg/kg/day of pure EGCG, given via oral gavage, would improve neurobehavioral and skeletal phenotypes in the Ts65Dn DS mouse model. Serum EGCG levels post-gavage were significantly higher in trisomic mice than in euploid mice. Daily EGCG gavage treatments over three weeks resulted in growth deficits in both euploid and trisomic mice. Compared to vehicle treatment, EGCG did not significantly improve behavioral performance of Ts65Dn mice in the multivariate concentric square field, balance beam, or Morris water maze tasks, but reduced swimming speed. Furthermore, EGCG resulted in reduced cortical bone structure and strength in Ts65Dn mice. These outcomes failed to support the therapeutic potential of EGCG, and the deleterious effects on growth and skeletal phenotypes underscore the need for caution in high-dose EGCG supplements as an intervention in DS.

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  • Ts65Dn male mice group housed and given chronic daily gavage of EGCG or vehicle for three weeks starting on P42 showed increased DYRK1A expression at P68 only in the cerebral cortex and not in the cerebellum or hippocampus.

    “In contrast, Ts65Dn male mice group housed and given chronic daily gavage of EGCG or vehicle for three weeks starting on P42 showed increased DYRK1A expression at P68 only in the cerebral cortex and not in the cerebellum or hippocampus (Goodlett et al., 2020).”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Goodlett et al., 2020

    The Results (DYRK1A protein levels; page unavailable) report higher DYRK1A protein levels in 68-day-old trisomic males only in the cerebral cortex, compared with euploid mice; EGCG had no significant effect. The Methods (Animals and EGCG treatment; pages unavailable) confirm group housing and daily EGCG or vehicle gavage from P42, but treatment continued through P68—about 26 days, not three weeks. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • DYRK1A expression in the trisomic system is not consistently upregulated 1.5-fold that of normal gene expression.

    “As we and others have previously described, DYRK1A expression in the trisomic system is not consistently upregulated 1.5-fold that of normal gene expression (Cheon et al., 2003; Goodlett et al., 2020; Stringer et al., 2017a).”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Goodlett et al., 2020

  • DYRK1A expression in the cerebellum, hippocampus, and cerebral cortex of 2 to 3-month Ts65Dn and control mice showed that DYRK1A was not overexpressed in the cerebellum or hippocampus but was overexpressed in the cerebral cortex of Ts65Dn mice.

    “DYRK1A expression in the cerebellum, hippocampus, and cerebral cortex of 2 to 3-month Ts65Dn and control mice showed that DYRK1A was not overexpressed in the cerebellum or hippocampus but was overexpressed in the cerebral cortex of Ts65Dn mice (Goodlett et al., 2020; Stringer et al., 2017a).”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Goodlett et al., 2020

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References 61 · Cited by 43

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Authors
Goodlett, C. R., Stringer, M., LaCombe, J., Patel, R., Wallace, J. M., & Roper, R. J.
Affiliations
  • Indiana University Indianapolis (US)
  • Indiana University – Purdue University Indianapolis (US)
Corresponding author
Roper, Randall J.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2020-06-26
Volume
10
Issue
1
Pages
10426-10426
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-020-67133-z
PMC
PMC7319987
OpenAlex
W3037763504
Cited by
43
References
61
Citations by year
2026: 5 · 2025: 6 · 2024: 5 · 2023: 9 · 2022: 9 · 2021: 8 · 2020: 1
FWCI
5.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion, cc-by)
  • Purdue University Indianapolis (Indiana University) (submittedVersion, cc-by)
  • PMC
Funders
  • Indiana University-Purdue University Indianapolis (UL1TR001108)
  • National Institutes of Health (UL1TR001108, HD090603)
  • National Center for Advancing Translational Sciences
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R15HD090603)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Tea Polyphenols and Effects
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
epigallocatechin gallate, Down syndrome, Ts65Dn mouse model, DYRK1A, green tea extract, neurobehavioral phenotype, skeletal phenotype, cortical bone strength, growth deficit, oral gavage, therapeutic interventions
MeSH terms
Cancellous Bone, Administration, Oral, Animals, Body Weight, Catechin, Disease Models, Animal, Down Syndrome, Femur, Treatment Outcome, Maze Learning, Mice, X-Ray Microtomography

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