Epigallocatechin-3-gallate attenuates impairment of learning and memory in chronic unpredictable mild stress-treated rats by restoring hippocampal autophagic flux.
Epigallocatechin gallate (EGCG) is a major polyphenol in green tea with beneficial effects on the impairment in learning and memory. Autophagy is a cellular process that protects neurons from stressful conditions. The present study was designed to investigate whether EGCG can rescue chronic unpredictable mild stress (CUMS)-induced cognitive impairment in rats and whether its protective effect involves improvement of autophagic flux. As expected, our results showed that CUMS significantly impaired memory performance and inhibited autophagic flux as indicated by elevated LC3-II and p62 protein levels. At the same time, we observed an increased neuronal loss and activated mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6k) signaling in the CA1 regions. Interestingly, chronic treatment with EGCG (25 mg/kg, i.p.) significantly improved those behavioral alterations, attenuated histopathological abnormalities in hippocampal CA1 regions, reduced amyloid beta1-42 (Aβ1-42) levels, and restored autophagic flux. However, blocking autophagic flux with chloroquine, an inhibitor of autophagic flux, reversed these effects of EGCG. Taken together, these findings suggest that the impaired autophagy in CA1 regions of CUMS rats may contribute to learning and memory impairment. Therefore, we conclude that EGCG attenuation of CUMS-induced learning and memory impairment may be through rescuing autophagic flux.
Department of Physiology & Institute of Neuroscience, University of South China, Hengyang, People's Republic of China; Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan, Hunan University of Chinese Medicine, Changsha, People's Republic of China.
Hong-Feng
HF
Gu
Department of Neurology of the First Affiliated Hospital, University of South China, Hengyang, People's Republic of China.
Ya-Xiong
YX
Nie
Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan, Hunan University of Chinese Medicine, Changsha, People's Republic of China.
Qiao-Zhen
QZ
Tong
Department of Physiology & Institute of Neuroscience, University of South China, Hengyang, People's Republic of China.
Ya-Ling
YL
Tang
Department of Neurology of the First Affiliated Hospital, University of South China, Hengyang, People's Republic of China.
Yang
Y
Zeng
Department of Neurology of the First Affiliated Hospital, University of South China, Hengyang, People's Republic of China.
Kai-Quan
KQ
Jing
Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan, Hunan University of Chinese Medicine, Changsha, People's Republic of China; Smooth Muscle Research Group, Department of Biochemistry & Molecular Biology, Libin Cardiovascular Institute of Alberta, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Xi-Long
XL
Zheng
Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan, Hunan University of Chinese Medicine, Changsha,Poeple's Republic of China.
Duan-Fang
DF
Liao
D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D002908:Chronic Disease; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D005786:Gene Expression Regulation; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018697:Nootropic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001324:Autoantigens; D002392:Catechin; D002738:Chloroquine; D008869:Microtubule-Associated Proteins; D018697:Nootropic Agents; D010446:Peptide Fragments; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C526109:Anxa3 protein, rat; C075222:amyloid beta-protein (1-42); C045651:epigallocatechin gallate; C546845:mTOR protein, rat