Combination of tea polyphenols and proanthocyanidins prevents menopause-related memory decline in rats via increased hippocampal synaptic plasticity by inhibiting p38 MAPK and TNF-α pathway

ABSTRACT

Objective

Many studies have examined the beneficial effects of tea polyphenols (TP) and proanthocyanidins (PC) on the memory impairment in different animal models. However, the combined effects of them on synaptic, memory dysfunction and molecular mechanisms have been poorly studied, especially in the menopause-related memory decline in rats.

Methods

In this rat study, TP and PC were used to investigate their protective effects on memory decline caused by inflammation. We characterized the learning and memory abilities, synaptic plasticity, AMPAR, phosphorylation of the p38 protein, TNF-ɑ, structural synaptic plasticity-related indicators in the hippocampus.

Results

The results showed that deficits of learning and memory in OVX + D-gal rats, which was accompanied by dendrites and synaptic morphology damage, and increased expression of Aβ1-42 and inflammation. The beneficial effects of TP and PC treatment were found to prevent memory loss and significantly improve synaptic structure and functional plasticity. TP+PC combination shows more obvious advantages than intervention alone. TP and PC treatment improved behavioral performance, the hippocampal LTP damage and the shape and number of dendrites, dendritic spines and synapses, reduced the burden of Aβ and decreased the inflammation in hippocampus. In addition, TP and PC treatment decreased the expressions of Iba-1, TNF-α, TNFR1, and TRAF2.

Conclusions

These results provided a novel evidence TP combined with PC inhibits p38 MAPK pathway, suppresses the inflammation in hippocampus, and increase the externalization of AMPAR, which may be one of the mechanisms to improve synaptic plasticity and memory in the menopause-related memory decline rats.

KEYWORDS:

• Tea polyphenols
• proanthocyanidins
• synaptic plasticity
• long-term potentiation
• AMPA receptor
• p38 MAPK
• microglia
• inflammation

Acknowledgements

The authors are indebted to QiaoNiu from Department of Occupational Hygiene of Shanxi Medical University for their electrophysiological measurements instruction.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Contributions

Haifeng Zhao and Qian Yang conceived and designed the study, Qian Yang performed the analyses and wrote the manuscript. Yusen Zhang, Luping Zhang, Xuemin Li, Ruirui Dong, Chenmeng Song, Le Cheng, Mengqian Shi helped collect and analyze the data. All authors read and approved the final manuscript.

Ethics approval

The animal care and experimental procedures were performed in accordance with the Guidelines for Animal Experimentation of Shanxi Medical University, with the approval of the Institutional Animal Care and Use Committee.(2014030).

Availability of data and materials

The raw/processed data required to reproduce these findings cannot be shared at this time as the data also forms part of an ongoing study. If you are interested, please contact the author.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant numbers 81973047; 81472984)]