Elsevier

Neuroscience

Volume 163, Issue 3, 20 October 2009, Pages 741-749
Neuroscience

Behavioural Neuroscience
Research Paper
Long-term green tea catechin administration prevents spatial learning and memory impairment in senescence-accelerated mouse prone-8 mice by decreasing Aβ1-42 oligomers and upregulating synaptic plasticity–related proteins in the hippocampus

https://doi.org/10.1016/j.neuroscience.2009.07.014Get rights and content

Abstract

The senescence-accelerated mouse prone-8 (SAMP8) is characterized by early onset of learning and memory deficits along with spontaneous overproduction of soluble β-amyloid peptide (Aβ) in the brain. In our study, 4 month old male SAMP8 mice were orally administered 0.05% and 0.1% green tea catechins (GTC, w/v) in drinking water for 6 months. We found that a supplementation with 0.05% or 0.1% GTC prevented spatial learning and memory impairments of mice in the Morris water maze. Better performance of GTC-treated mice was associated with decreased levels of Aβ1-42 oligomers in the hippocampus. The activity of the protein kinase A/cAMP-response element binding protein (PKA/CREB) pathway, one of the molecular targets of Aβ oligomers which is crucial for late long-term potentiation and long-term memory formation, was significantly increased after GTC administration. We also found that chronic 0.05% or 0.1% GTC consumption prevented the reductions of three representative proteins of synaptic function and synaptic structure, including brain-derived neurotrophic factor(BDNF), post-synaptic density protein-95 (PSD95) and Ca2+/calmodulin-dependent protein kinase II (CaMKII). These results demonstrated that long-term 0.05% or 0.1% green tea catechin administration may prevent spatial learning and memory decline of SAMP8 mice by decreasing Aβ1-42 oligomers and upregulating synaptic plasticity–related proteins in the hippocampus.

Section snippets

Animals and supplementation

Male SAMP8 and accelerated senescence-resistant mouse prone-1 (SAMR1) mice were provided by the Department of Laboratory Animal Science of Peking University Health Science Center. Each mouse was individually housed per cage with a 12-h light/dark cycle under controlled temperature (23±2 °C) and humidity (50±10%). The animals had free access to food and water. After a 7 day acclimatization to the laboratory conditions, 4 month old SAMP8 mice (n=45) were randomly divided into three groups: SAMP8

GTC intake and body weights

Daily water intake per mouse did not differ among the SAMP8 control (5.39±0.20 ml/day), SAMR1 control (5.11±0.17 ml/day), 0.05% GTC-treated (5.40±0.21 ml/day) and 0.1% GTC-treated (5.15±0.22 ml/day) groups. The mean dose of GTC was therefore calculated to be about 75 and 150 mg/kg/day. Body weights of mice submitted to GTC treatment were similar to that of the SAMP8 control mice both at the beginning (SAMP8: 34.21±0.45 g; 0.05% GTC: 34.52±0.75 g; 0.1% GTC: 34.14±0.55 g) and at the end of the

Discussion

Recently, SAMP8 mice have drawn attention in gerontological research of dementia due to their characteristic early onset of cognitive deficits (Butterfield and Poon, 2005). SAMR1 mice, which are genetically related to SAMP8 but resistant to accelerated senescence, have always been used as normal control (Tajes et al., 2008). Previous studies indicated that SAMP8 mice show decrement of spatial learning and memory in MWM emerging at 8 months of age and deteriorate from then on (Chen et al., 2007

Conclusion

In conclusion, the primary finding of this study is that chronic GTC treatment may prevent spatial memory deficits in aged SAMP8 mice by modulating the Aβ cascade. Thus, drinking tea every day might be an effective habit in preventing the onset of AD and in ameliorating the memory defects in the early phases of the disease.

Acknowledgments

This work was supported by the foundation (No. 2006BAD27B08) from the Ministry of Science and Technology of the People's Republic of China.

References (46)

  • A.M. Haque et al.

    Long-term administration of green tea catechins improves spatial cognition learning ability in rats

    J Nutr

    (2006)
  • Q. Li et al.

    Long-term administration of green tea catechins prevents age-related spatial learning and memory decline in C57BL/6J mice by regulating hippocampal cyclic AMP-response element binding protein signaling cascade

    Neuroscience

    (2009)
  • S. Mandel et al.

    Iron dysregulation in Alzheimer's disease: multimodal brain permeable iron chelating drugs, possessing neuroprotective-neurorescue and amyloid precursor protein-processing regulatory activities as therapeutic agents

    Prog Neurobiol

    (2007)
  • A.C. McKee et al.

    Ibuprofen reduces Abeta, hyperphosphorylated tau and memory deficits in Alzheimer mice

    Brain Res

    (2008)
  • J.E. Morley et al.

    Beta-amyloid precursor polypeptide in SAMP8 mice affects learning and memory

    Peptides

    (2000)
  • D.F. Obregon et al.

    ADAM10 activation is required for green tea (-)-epigallocatechin-3-gallate-induced alpha-secretase cleavage of amyloid precursor protein

    J Biol Chem

    (2006)
  • S. Oddo et al.

    Temporal profile of amyloid-beta (Abeta) oligomerization in an in vivo model of Alzheimer diseaseA link between Abeta and tau pathology

    J Biol Chem

    (2006)
  • P.T. Pang et al.

    Regulation of late-phase LTP and long-term memory in normal and aging hippocampus: role of secreted proteins tPA and BDNF

    Ageing Res Rev

    (2004)
  • A.L. Petursdottir et al.

    Lipid peroxidation in brain during aging in the senescence-accelerated mouse (SAM)

    Neurobiol Aging

    (2007)
  • C. Ramassamy

    Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets

    Eur J Pharmacol

    (2006)
  • D.J. Selkoe

    Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior

    Behav Brain Res

    (2008)
  • H. Taguchi et al.

    Catalytic antibodies to amyloid beta peptide in defense against Alzheimer disease

    Autoimmun Rev

    (2008)
  • T. Takeda et al.

    A new murine model of accelerated senescence

    Mech Ageing Dev

    (1981)
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