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1. Chitinase-1 Reduces Microglia Inflammation Through The HDAC3/NF-?B Pathway In A Rat Model Of Cognitive Impairment; 2. Analysis Of The Compliance And Medication Status Of Anti-dementia Drugs Based On Memory Impairment Clinics

Posted on:2021-03-07Degree:MasterType:Thesis
Country:ChinaCandidate:X Y YuFull Text:PDF
GTID:2434330620975041Subject:Geriatrics
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Objective: Histone deacetylase 3(HDAC3)plays an important role in the expression and regulation of proteins involved in the pathophysiology of Alzheimer's disease(AD).Activation of the nuclear factor-?B(NF-?B)signaling pathway in neurons has been implicated in the progression of AD.NF-?B activation is regulated by HDAC acylation.Chitinase-1(CHIT1,chitinase1)is elevated in cerebrospinal fluid and peripheral blood of AD patients.We have previously shown that CHIT1 provides potential protection through microglial polarization and reduced ?-amyloid(A?)accumulation in a rat model of cognitive impairment.The aim of this experiment was to investigate the role of CHIT1 in HDAC3/NF-?B signaling in D-galactose(D-gal)and aluminum trichloride(AlCl3)-induced cognitive impairment models.Methods: Twenty-eight SD rats were randomly divided into 2 groups:control(n = 7)and AD-like pathologies model(n = 21).A subacute AD-like pathologies model was induced by continuous intraperitoneal injection of D-gal and AlCl3 for 90 days.The AD-like model group was randomly divided into three groups and injected with the correspondingintervention reagents.Morris water maze was used to detect the cognitive function of rats in each group.Western blot was used to detect the expression levels of HDAC3,NF-?B,I?B?,and iNOS.qRT-PCR was used to detect the gene expression levels of HDAC3,NF-?B,iNOS,IL-1?,TNF-?,Arg-1,IL-10,and CD206.Immunohistochemistry was used to detect the expression of NF-?B.Results: After treated with CHIT1,the protein and mRNA levels of HDAC3 and NF-?B were decreased,the expression level of I?B? was increased,the anti-inflammatory markers(Arg-1,IL-10 and CD206)were increased,and the pro-inflammatory markers(TNF-a,iNOS and IL-1?)were decreased in D-gal/AlCl3-induced AD-like rats.Conclusions: CHIT1 can regulate microglial polarization via HDAC3/NF-?B p65 pathway,contributing to improvement of cognitive impairment.Purpose: To investigate the use and adherence of anti-dementia drugs in elderly patients with dementia from the Memory Clinic of The First Affiliated Hospital of Chongqing Medical University.Methods: Patients were recruited from the Memory Clinic of The First Affiliated Hospital of Chongqing Medical University between December 2010 and December 2018.The medical chart was reviewed,including diagnosis,dosage of antidementia medicine,neuropsychological testing scores,and the further questionnaires were conducted via face-to-face or telephone,included duration of treatment,types of anti-dementia drugs,and reasons for treatment discontinuation.Results: The data from 422 patients were analyzed retrospectively for this study.315 were diagnosed with AD,67 with MCI,and 40 with other types of dementia.From the 422 patients,26.8% were treated with original donepezil,11.6% with generic donepezil,24.6% with memantine,13.3%with huperzine A,and 23.7% with a combination of drugs.However,73%of patients discontinued treatment within one year of initiation.Patients treated for more than 36 months(37.8%)were more likely to choose combined medication,as compared with patients treated for less than 36 months.Patients with less than nine years of education(OR: 2.394;95% CI:1.508,3.801)were more likely to discontinue treatment than patients with more than nine years of education.Patients with elevated PSMS scores(OR: 1.195;95% CI: 1.086,1.316)had a high risk of discontinuation.Conclusions: Overall treatment compliance is relatively poor in memory clinic in Chongqing.Our study demonstrates that higher education may lead to better treatment adherence in dementia care.Combination therapy may increase treatment time.However,poorer PSMS is a significant risk factor for treatment discontinuation.
Keywords/Search Tags:Alzheimer's disease, chitotriosidase, HDAC3, microglial polarization, NF-?B p65, adherence, anti-dementia drugs, daily living activities, dementia, education
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