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Epigallocatechin-3-gallate attenuates impairment of learning and memory in chronic unpredictable mild stress-treated rats by restoring hippocampal autophagic flux.

Gu HF, Nie YX, Tong QZ, Tang YL, Zeng Y, Jing KQ, Zheng XL, Liao DF - PLoS ONE (2014)

Bottom Line: 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.Therefore, we conclude that EGCG attenuation of CUMS-induced learning and memory impairment may be through rescuing autophagic flux.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

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EGCG treatment reduces both soluble and insoluble Aβ1–42 levels in the hippocampal CA1 regions of CUMS rats.(A) The soluble Aβ1–42 levels in different groups were detected by ELISA. Data were presented as (pg/mg protein). (B) Insoluble Aβ1–42 levels in different groups were measured by ELISA. Data were presented as (ng/mg protein). Control, control group; CUMS, chronic unpredictable mild stress group; CUMS + CQ, CQ administration followed by CUMS group; CUMS + EGCG, EGCG treatment followed by CUMS group; CUMS + EGCG + CQ, co-administration with EGCG and CQ followed by CUMS group; Vehicle, vehicle treatment followed by CUMS group. The drugs (EGCG and CQ) were given to rats 30 min before the stress exposure. Data are shown as mean ± SEM (n = 4 for each group). *P<0.05 versus CUMS group, #P<0.05 versus CUMS + EGCG group.
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pone-0112683-g006: EGCG treatment reduces both soluble and insoluble Aβ1–42 levels in the hippocampal CA1 regions of CUMS rats.(A) The soluble Aβ1–42 levels in different groups were detected by ELISA. Data were presented as (pg/mg protein). (B) Insoluble Aβ1–42 levels in different groups were measured by ELISA. Data were presented as (ng/mg protein). Control, control group; CUMS, chronic unpredictable mild stress group; CUMS + CQ, CQ administration followed by CUMS group; CUMS + EGCG, EGCG treatment followed by CUMS group; CUMS + EGCG + CQ, co-administration with EGCG and CQ followed by CUMS group; Vehicle, vehicle treatment followed by CUMS group. The drugs (EGCG and CQ) were given to rats 30 min before the stress exposure. Data are shown as mean ± SEM (n = 4 for each group). *P<0.05 versus CUMS group, #P<0.05 versus CUMS + EGCG group.

Mentions: Excessive accumulation of Aβ peptide in the brain is the key pathological change in AD-like cognitive dysfunction. Considering the crucial role of autophagy in Aβ1–42 production, we determined the effect of EGCG on the accumulation of Aβ1–42 in the hippocampal CA1 region by ELISA analysis. As shown in Fig. 6, the soluble (Fig. 6A) and insoluble Aβ1-42 (Fig. 6B) levels in the CA1 regions of the different groups were measured by ELISA, respectively. The results showed that both soluble and insoluble Aβ1–42 contents in the CA1 of CUMS group rats were significantly higher than those of control ones (P<0.05, Fig. 6A, B). Aβ1–42 levels in the CA1 of CUMS + CQ group were much higher than those in CUMS group (P<0.05, Fig. 6A, B). As expected, treatment of EGCG obviously decreased such a high level of Aβ1–42 in the CA1 areas of CUMS (P<0.05, Fig. 6A, B), while CQ could reverse the EGCG-induced Aβ1–42 reduction in CA1 regions of CUMS rats (P<0.05, Fig. 6A, B). This result thereby suggested that EGCG decreased Aβ1–42 levels and via restoring autophagic flux.


Epigallocatechin-3-gallate attenuates impairment of learning and memory in chronic unpredictable mild stress-treated rats by restoring hippocampal autophagic flux.

Gu HF, Nie YX, Tong QZ, Tang YL, Zeng Y, Jing KQ, Zheng XL, Liao DF - PLoS ONE (2014)

EGCG treatment reduces both soluble and insoluble Aβ1–42 levels in the hippocampal CA1 regions of CUMS rats.(A) The soluble Aβ1–42 levels in different groups were detected by ELISA. Data were presented as (pg/mg protein). (B) Insoluble Aβ1–42 levels in different groups were measured by ELISA. Data were presented as (ng/mg protein). Control, control group; CUMS, chronic unpredictable mild stress group; CUMS + CQ, CQ administration followed by CUMS group; CUMS + EGCG, EGCG treatment followed by CUMS group; CUMS + EGCG + CQ, co-administration with EGCG and CQ followed by CUMS group; Vehicle, vehicle treatment followed by CUMS group. The drugs (EGCG and CQ) were given to rats 30 min before the stress exposure. Data are shown as mean ± SEM (n = 4 for each group). *P<0.05 versus CUMS group, #P<0.05 versus CUMS + EGCG group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231069&req=5

pone-0112683-g006: EGCG treatment reduces both soluble and insoluble Aβ1–42 levels in the hippocampal CA1 regions of CUMS rats.(A) The soluble Aβ1–42 levels in different groups were detected by ELISA. Data were presented as (pg/mg protein). (B) Insoluble Aβ1–42 levels in different groups were measured by ELISA. Data were presented as (ng/mg protein). Control, control group; CUMS, chronic unpredictable mild stress group; CUMS + CQ, CQ administration followed by CUMS group; CUMS + EGCG, EGCG treatment followed by CUMS group; CUMS + EGCG + CQ, co-administration with EGCG and CQ followed by CUMS group; Vehicle, vehicle treatment followed by CUMS group. The drugs (EGCG and CQ) were given to rats 30 min before the stress exposure. Data are shown as mean ± SEM (n = 4 for each group). *P<0.05 versus CUMS group, #P<0.05 versus CUMS + EGCG group.
Mentions: Excessive accumulation of Aβ peptide in the brain is the key pathological change in AD-like cognitive dysfunction. Considering the crucial role of autophagy in Aβ1–42 production, we determined the effect of EGCG on the accumulation of Aβ1–42 in the hippocampal CA1 region by ELISA analysis. As shown in Fig. 6, the soluble (Fig. 6A) and insoluble Aβ1-42 (Fig. 6B) levels in the CA1 regions of the different groups were measured by ELISA, respectively. The results showed that both soluble and insoluble Aβ1–42 contents in the CA1 of CUMS group rats were significantly higher than those of control ones (P<0.05, Fig. 6A, B). Aβ1–42 levels in the CA1 of CUMS + CQ group were much higher than those in CUMS group (P<0.05, Fig. 6A, B). As expected, treatment of EGCG obviously decreased such a high level of Aβ1–42 in the CA1 areas of CUMS (P<0.05, Fig. 6A, B), while CQ could reverse the EGCG-induced Aβ1–42 reduction in CA1 regions of CUMS rats (P<0.05, Fig. 6A, B). This result thereby suggested that EGCG decreased Aβ1–42 levels and via restoring autophagic flux.

Bottom Line: 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.Therefore, we conclude that EGCG attenuation of CUMS-induced learning and memory impairment may be through rescuing autophagic flux.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus