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Effect Of Curcumin On Cognitive And Memory Function In App/PS1 Mice

Posted on:2021-01-29Degree:MasterType:Thesis
Country:ChinaCandidate:J L ChenFull Text:PDF
GTID:2504306113478274Subject:Biochemistry and Molecular Biology
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Alzheimer’s disease(AD)is a neurodegenerative disease that affects people over the age of 65 years old and causes patient-related emotional,social,and economic burdens.The main feature of AD is the aggregation of Aβinto senile plaques and the formation of nerve fiber tangles.At present,the pathogenesis of AD is mainly attributed to Aβ deposition,and effective therapeutic drugs have not yet been available.Studies have reported that curcumin has shown beneficial effects on brain health through a variety of mechanisms,such as antioxidants,beta amyloid binding,anti-inflammatory,metal chelation,and promoting neurogenesis.In particular,it can improve cognitive and memory dysfunction in AD models.To study the ability of curcumin in learning and memory,spatial exploration ability of hippocampus,cortex β amyloid deposition,the number of hippocampal CA1 and CA3 Neu N positive cells and the expression of hippocampal and cortical memory-related proteins.Attempts were made to verify the mechanism of curcumin intervention in APP /PS1 model mice through multiple indicators.Four-month-old APP / PS1 mice were randomly divided into five groups which include a WT control group,an AD model group.a low curcumin concentration group(100 mg /kg),a high curcumin concentration group(300 mg / kg),and a positive drug control group.After intraperitoneal injection of curcumin for 7 consecutive days,changes in body weight of the mice were recorded,and neurobehavioral assessment of the mice’s spatial learning and memory abilities.Brain tissues were taken for histological evaluation,the levels of hippocampal and cortical Aβ were detected by immunohistochemistry,and the expression of Neu N positive cells in hippocampal CA1 and CA3 regions was detected by immunofluorescence staining.Western blot was used to detect the expression of CREB,pCREB and BDNF in hippocampal and cortical memory formation.The following results were obtained in this study.(1)The genetic identification and confirmation of APP / PS1 mice was positive.Behavioral evaluation indicated that the escape latency of APP / PS1 double transgenic mice was significantly longer than that of WT mice(P <0.001).The number of cross-platforms within 2 minutes of WT mice was more than that of APP / PS1 double transgenic mice(P <0.001);(2)After one week of continuous administration,analysis of body weight records showed that there was no difference in small body weight compared with WT mice(P > 0.05);(3)One week after curcumin intervention,Morris-water maze behavioral test showed that compared with the AD model group,the memory and space exploration ability of APP / PS1 mice was enhanced after curcumin intervention.The new object recognition experiment showed that compared with the model group,the new object recognition index of APP / PS1 mice increased after curcumin intervention;(4)Immunohistochemical analysis showed that after curcumin intervention,the hippocampus and cortex A β expression in APP / PS1 mice was significantly decreased(P <0.01);(5)In immunofluorescence experiments,compared with the model group,the expression of Neu N positive cells in hippocampal CA1 and CA3 regions of APP / PS1 mice was significantly increased after curcumin intervention(P <0.05);The our results showed that compared with the model group,the expressions of BDNF and p-CREB in the hippocampus and cortex of the curcumin-treated group was all significantly increased(P <0.01).Our study showed that curcumin can effectively reduce the deposition of Aβ in the hippocampus and cortex of APP / PS1 mice,increase the number of Neu N positive cells in the hippocampal CA1 and CA3 regions,and improve memory and cognitive functions of APP / PS1 mice.
Keywords/Search Tags:Curcumin, Alzheimer’s disease, APP/PS1 double trangenic mouse, BDNF, amyloid-β, CREB, Memory disorders
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