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Cognitive ameliorating effect of fermented Perilla frutescens on sleep deprivation-induced cognitive impairment

초록/요약

Perilla frutescens (PF) is a traditional medicine herb in East Asian countries. In present study, we evaluated the effects of fermented PF (FPF) in sleep deprivation induced cognitive impairment model. The mice were pretreated with FPF for 3 days via oral administration before sleep deprivation (SD) for 72 h. SD impaired cognitive function and these results were restored by FPF administration in mice. Also, SD exposure significantly increased cellular oxidative damage and neuronal cell death in hippocampus. FPF may prevented this impairment in hippocampus. Furthermore, the FPF inhibited glutamate-induced both cell death and ROS accumulation in hippocampal neuron cells in vitro. Also, we confirmed FPF has radical scavenging activities in both DPPH and ABTS assay. These founding indicated that FPF has antioxidant and neuroprotective effects through radical scavenging activities. Additionally, SD exposure decreased the level of brain-derived nerve growth factor (BDNF) and regained by FPF treatment. We evaluated to these changes whether associated with cognitive improvement effect of FPF at behavior test. The treatment of TrkB antagonist was significantly abolished cognitive abilities and hippocampal neuronal cell survival in FPF-treated mice. These results suggest that FPF has a therapeutic potential for cognitive improvement by regulating oxidative stress and activation of BDNF/TrkB signaling pathway. Therefore, FPF could be used as a novel herbal medicine for the treatment of cognitive and memory function.

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목차

Ⅰ. INTRODUCTION 1
A. Sleep and Cognition 1
B. Sleep deprivation (SD)-induced hippocampal oxidative stress 2
C. BDNF/TrkB signaling pathway on cognitive function 3
D. Fermented Perilla frutescens 3
E. Aims of study 4
Ⅱ. MATERIALS AND METHODS 5
A. Reagents 5
B. Preparation of FPF 5
C. Animals 6
D. Sleep deprivation-induced cognitive impairment model 7
E. Y-maze 7
F. Passive avoidance 8
G. Preparation of brain sample 8
H. Measurement of oxidative stress markers 9
I. Western blotting 9
J. Hematoxylin and Eosin (H&E) staining 10
K. Cell culture 11
L. Cell viability assay 11
M. Measurement of reactive oxygen species 12
N. DPPH Radical scavenging activity 12
O. ABTS Radical scavenging activity 13
P. Statistical analysis 13
Ⅲ. RESULTS 14
A. FPF improves learning and memory abilities in sleep-deprived mice 14
B. FPF attenuates hippocampal oxidative stress in sleep-deprived mice 17
C. FPF-induced memory improvement effect was mediated by BDNF/TrkB pathway activation 19
D. FPF increased hippocampal neuronal cell survival in sleep-deprived mice 22
E. Neuroprotective effect of FPF on glutamate-induced cell death in HT-22 cells 25
F. Antioxidant effect of FPF on glutamate-induced oxidative stress in HT-22 cells 28
G. Antioxidant effects of FPF in vitro 30
IV. DISCUSSION 32
V. CONCLUSION 38
REFERENCES 39

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