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Curcumin on APP/PS1 double transgenic mice AD7C -NTP IGF1R and ChAT expression
Author: LiRuiZuo
Tutor: WangPengWen
School: Beijing University of Traditional Chinese Medicine
Course: Traditional Chinese Medicine
Keywords: Alzheimer's disease Curcumin APP/PS1 double transgenic mice Choline acetyltransferase Insulin-like growth factor 1 receptor Neurofilament protein related to Alzheimer's disease
CLC: R285.5
Type: Master's thesis
Year: 2011
Downloads: 75
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Abstract
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The purpose of Alzheimer's disease (Alzheimer's disease, AD) is a kind of early cognitive dysfunction and neuronal lesions based diseases. Characteristic pathological changes in the performance of the beta-amyloid peptide (amyloid beta, Aβ) aggregate to form senile plaques (senile plaques, SPs), highly phosphorylated tau protein in the form of neurofibrillary tangles (neurofibrillary tangles NFTs) neurons and synaptic loss and dysfunction of cholinergic neurons. AD the current lack of effective methods for early diagnosis and drug treatment, the latest research shows that Chinese medicine monomer have neuroprotective effects of curcumin, finding that the development of safe and effective prevention and treatment of AD drugs as possible. This research aims to detect APP/PS1 double transgenic mice urine AD7C-NTP content, improve the situation of the dynamic effects of curcumin neuropathological changes in AD model mice, the experiment also combined with immunohistochemical staining from morphological observation of these indicators, the brain AD7C-NTP, IGF1R and ChAT expression and the distribution, · and application of Western-blot method for semi-quantitative, to further explore the molecular mechanisms of the neuroprotective effect of curcumin. Materials and Methods. APP/PS1 double transgenic mice and normal mice of the same background in the same months of age as experimental subjects, 12 in each group. Chinese medicine curcumin, small dose group of 3-month-old mice, gavage treatment, rosiglitazone group given rosiglitazone orally once a day. The above set of continuous treatment for three months. Application jumping experimental test APP/PS1 double transgenic mice learning and memory and memory retention, evaluation curcumin APP/PS1 double transgenic mice cognitive abilities. 3 APP/PS1 double transgenic mice urine AD7C-NTP content using enzyme-linked immunosorbent assay (ELISA) detection, of dynamic observation curcumin mice AD ??disease progression. 4 APP/PS1 double transgenic mice by curcumin treatment the brain AD7C-NTP, IGF1R and ChAT expression changes observed using immunohistochemistry and Western-blot method, to explore the possible mechanism of action of curcumin neuroprotection. Experimental results. Curcumin APP/PS1 double transgenic mice learning and memory, and memory retention capacity, the number of errors affect the mice jumping experimental training period, each group of mice with the normal control group (CON) mice compared with the model group ( APP/PS1 VEH) mice and the number of errors increased significantly (P lt; 0.01). Test period the number of errors mice compared with CON mice, the number of errors of APP/PS1 VEH mice was significantly increased (P lt; 0.01);, curcumin with APP/PS1 VEH than low-dose group (APP/PS1 Curcumin- L) mice decrease in the number of errors (P lt; 0.05), rosiglitazone group (APP/PS1 RSG) Curcumin high-dose group (APP/PS1 Curcumin-H), curcumin middle dose group (APP/PS1 Curcumin- M) the number of errors were significantly reduced (P lt; 0.01). Trial period latency mice measured compared with CON mice, APP/PS1 VEH mouse latency time significantly reduce (P lt; 0.01); with the compared to APP/PS1 VEH mice, the APP/PS1 Curcumin-H The APP/PS1 Curcumin-L mice Latency increased (P lt; 0.05), The APP/PS1 RSG of APP/PS1 Curcumin-M latency in mice significantly increased (P lt; 0.01). At different time points. The dynamic observation curcumin APP/PS1 double transgenic mice urine AD7C-NTP content expressed urine of mice in each group AD7C-NTP concentration change, the results showed that after one month of treatment, the mice in each group urine AD7C-NTP concentration, except APP/PS1 VEH, the rest of the group was no significant difference compared with before treatment; 3 months of treatment with 2 months of treatment compared to APP/PS1 RSG the APP/PS1 Curcumin- H, APP / P S1 Curcumin-M mice urine AD7C-NTP concentration continues to decline and a significant difference (P lt; 0.01), the APP/PS1 Curcumin-L mice no difference (P gt; 0.05) . The same time points mice urine AD7C-NTP concentration group comparison, the results showed that the mice in each group before drug intervention APP/PS1 RSG, of APP/PS1 Curcu min-H, of APP/PS1 Curcumin-M APP/PS1 of Curcumin-L APP/PS1 VEH was no significant difference; 3 months after treatment, compared to APP/PS1 RSG the APP/PS1 Curcumin-H of APP/PS1 Curcumin-M APP/PS1 VEH mice urine AD7C -NTP levels have decreased and a significant difference (P lt; 0.05, P lt; 0.01) APP/PS1 Curcumin-L compared with CON mice urine AD7C-NTP content was increased and there is a significant difference ( P lt; 0.05) 3. effects of curcumin on the expression of APP/PS1 double transgenic mice the brain AD7C-NTP, IGF1R and ChAT content immunohistochemical staining results: of APP/PS1 VEH mice compared with CON mice hippocampal CA1 District ChAT and IGF1R positive cells significantly reduced (P lt; 0.01), number of AD7C-NTP-positive cells increased significantly (P lt; 0.01); the APP/PS1 Curcumin-H APP/PS1 the Curcumin-L mouse hippocampal CA1 region ChAT IGF1R positive cells also decreased compared with CON mice (P lt; 0.05), while the increase in the number of positive cells AD7C-NTP (P lt; 0.05); compared with APP/PS1 VEH the APP/PS1 Curcumin-M Hekou APP / PS1 RSG mouse hippocampal CA1 region of ChAT IGF1R the number of positive cells increased (P lt; 0.05 and P lt; 0.01)-NTP-positive cells AD7C number of reduce (P gt; 0.05). Motic image analysis system of APP/PS1 VEH and APP/PS1 Curcumin-L mouse hippocampal CA1 region ChAT and IGF1R cells mean gray value than CON average gray value of mouse cells increased significantly (P lt; 0.01), the other group compared with the CON mice there was no difference; APP/PS1 VEH mice compared to the of APP/PS1 Curcumin-M, and APP/PS1 RSG mice ChAT cells significantly reduced the average gray value (P lt; 0.01), AD7C- NTP result of its opposite. Western blot results: AD7C-NTP, IGF1R and ChAT protein expression results immunohistochemistry of the match. Conclusion Curcumin can enhance ChAT activity by regulating IGF1R expression to inhibit the generation of AD7C-NTP to achieve to delay AD disease progression and improve the purpose of learning and memory in AD model.
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