Modified (-)-gallocatechin gallate-enriched green tea extract rescues age-related cognitive deficits by restoring hippocampal synaptic plasticity

Aging leads to cognitive impairments characterized by reduced hippocampal functions that are associated with impairment of long-term potentiation of CA1 synapses. Here, we assessed the safety and efficacy of modified (-)-gallocatechin gallate (GCG)-enriched green tea extract (HTP-GTE) in ameliorating the cognitive dysfunctions in late middle-aged murine model. We developed a novel HTP-GTE that was enriched with GCG via epimerization that involved heating. We compared the effects of oral administrations of conventional green tea and HTP-GTE in young and aged male C57/BL6 mice, and examined the changes in the hippocampal functions related to aging process. The functional outcome was assessed by the electrophysiological experiments to measure the long-term potentiation (LTP). HTP-GTE improved the age-related cognitive impairments via restoring long-term synaptic plasticity. We also identified that GCG was the main active component responsible for the HTP-GTE effect. The main molecular pathway in ameliorating the age-related cognitive dysfunctions involved protein kinase A (PKA) which was shown to be modulated by HTP-GTE. Thus, HTP-GTE has a therapeutic potential as a dietary supplement which may aid to rescue the impaired cognitive functions at the early phase of aging process through the modulation of LTP threshold.

Aging; DIC, differential interference contrast; DMSO, dimethyl sulfoxide; EGCG, (−)-epigallocatechin-3-gallate; GCG, (−)-gallocatechin gallate; GTE, conventional green tea extract; HPLC-PDA, high performance liquid chromatography photometric diode array; HTP-GTE, GCG-enriched green tea extract; Hippocampus; LTP, long-term potentiation; Long-term potentiation; MTT, methylthiazolyldiphenyl-tetrazolium bromide; MWM, Morris water maze; Memory; NMDARs, N-Methyl-d-aspartate receptors; PKA, protein kinase A; SC, Schaffer collateral; TTX, tetrodotoxin; aCSF, artificial cerebrospinal fluid; fEPSPs, field excitatory postsynaptic potentials; −)-Gallocatechin gallate.