NeuroMolecular Medicine

, Volume 18, Issue 3, pp 378–395 | Cite as

Effects of Grape Skin Extract on Age-Related Mitochondrial Dysfunction, Memory and Life Span in C57BL/6J Mice

  • Heike Asseburg
  • Carmina Schäfer
  • Madeleine Müller
  • Stephanie Hagl
  • Maximilian Pohland
  • Dirk Berressem
  • Marta Borchiellini
  • Christina Plank
  • Gunter P. Eckert
Original Paper
First Online:
Received:
Accepted:

Abstract

Dementia contributes substantially to the burden of disability experienced at old age, and mitochondrial dysfunction (MD) was identified as common final pathway in brain aging and Alzheimer’s disease. Due to its early appearance, MD is a promising target for nutritional prevention strategies and polyphenols as potential neurohormetic inducers may be strong neuroprotective candidates. This study aimed to investigate the effects of a polyphenol-rich grape skin extract (PGE) on age-related dysfunctions of brain mitochondria, memory, life span and potential hormetic pathways in C57BL/6J mice. PGE was administered at a dose of 200 mg/kg body weight/d in a 3-week short-term, 6-month long-term and life-long study. MD in the brains of aged mice (19–22 months old) compared to young mice (3 months old) was demonstrated by lower ATP levels and by impaired mitochondrial respiratory complex activity (except for mice treated with antioxidant-depleted food pellets). Long-term PGE feeding partly enhanced brain mitochondrial respiration with only minor beneficial effect on brain ATP levels and memory of aged mice. Life-long PGE feeding led to a transient but significant shift of survival curve toward higher survival rates but without effect on the overall survival. The moderate effects of PGE were associated with elevated SIRT1 but not SIRT3 mRNA expressions in brain and liver tissue. The beneficial effects of the grape extract may have been influenced by the profile of bioavailable polyphenols and the starting point of interventions.

Keywords

Brain aging Mitochondria Grape polyphenols Memory Life span Hormesis 
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Notes

Acknowledgments

The polyphenol-rich grape skin extract was kindly provided by Breko GmbH, Bremen, Germany, and was analyzed by the group of Prof. P. Winterhalter, Institute of Food Chemistry, Braunschweig University of Technology, Germany. This work was funded by the Alzheimer Forschung Initiative e.V. (Grant No. #14838).

Compliance with Ethical Standards

Conflicts of interest

The authors state that they have no conflict of interest.

Animal Rights

All animal studies were approved by the local authorities for animal welfare, and all experiments were carried out according to the European Communities Council Directive (86/609/EEC) by individuals with appropriate training.

Supplementary material

12017_2016_8428_MOESM1_ESM.eps (513 kb)
Relative normalized mRNA expression of antioxidant enzymes in brain (a-c) and liver (d-f) tissue from mice of the long-term (LT) study determined using quantitative real-time PCR. For more information on the design of the studies please refer to Fig. 1. Data represent mean ± SEM normalized on mean mRNA expression of young mice (100 %), n = 10, SOD2: super dismutase 2, CAT: catalase, GPx1: glutathione peroxidase 1 (EPS 512 kb)
12017_2016_8428_MOESM2_ESM.pdf (202 kb)
Supplementary material 2 (PDF 202 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Heike Asseburg
    • 1
    • 2
  • Carmina Schäfer
    • 1
  • Madeleine Müller
    • 3
  • Stephanie Hagl
    • 1
  • Maximilian Pohland
    • 1
  • Dirk Berressem
    • 1
  • Marta Borchiellini
    • 4
  • Christina Plank
    • 1
  • Gunter P. Eckert
    • 1
    • 2
  1. 1.Department of Pharmacology, Biocenter Campus RiedbergGoethe-University of FrankfurtFrankfurtGermany
  2. 2.Institute of Nutritional SciencesUniversity of GiessenGiessenGermany
  3. 3.Provadis School of International Management and Technology AGFrankfurtGermany
  4. 4.Department of Pharmaceutical SciencesUniversity of PerugiaPerugiaItaly

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