Yishen Huazhuo Decoction induces autophagy to promote the clearance of Aβ1-42 in SAMP8 mice: mechanism research of a traditional Chinese formula against Alzheimer’s disease
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Yishen Huazhuo Decoction induces autophagy to promote the clearance of Aβ1-42 in SAMP8 mice: mechanism research of a traditional Chinese formula against Alzheimer’s disease
Background: Studies have found that autophagy can promote clearance of Aβ. To promote and maintain the occurrence of autophagy in Alzheimer’s disease (AD) may be a potential way to reduce neuronal loss and improve learning and memory of AD.
Objective: To investigate the possible mechanism of Yishen Huazhuo Stew (YHD) for the model of AD.
Methods: Forty-seven-month-old male SAMP8 mice were randomly divided into the model (P8) YHD groups and groups, 20 in each group, with 20 SAMR1 rats as control (R1) group. All the mice were intragastric administered for 4 weeks, YHD at a dose of 6.24g / kg for YHD group, and distilled water to P8 groups and R1 group. Morris water maze (MWM) test, staining Nissl’s, TEM, TUNEL staining, immunofluorescence staining double, and western blot analysis were applied to learning and memory, structure and ultrastructure of neurons, autophagosome, the apoptotic index, Aβ, LAMP1, and autophagy-associated protein ,
Results: The escape latency time YHD group was significantly shorter in the 4 and 5 days for the test MWM than P8 group (P = 0.011, 0.008 <0.05), and the number of crossing platform in YHD group increased significantly (P = 0, 02 <0.05). Nissl staining showed that the number of neurons in YHD group increased significantly (P <0.0001). TEM shows in YHD group, the nucleus of neurons slightly irregular, with slightly reduced organelles, partially fused and blurred crest and the mitochondrial membrane.
YHD group apoptosis index showed a downward trend, with no statistically significant difference (P = 0.093> 0.05), whereas the expression Caspase3 YHD group was significantly lower (P = 0.044 <0.05). YHD can promote clearance of Aβ1-42 protein, upregulated Beclin-1 and p-Bcl-2 protein, reducing the protein mTOR and P62.
Conclusion: YHD can induce autophagy initiation, increasing the formation of autophagosomes and autolysosome, promoting autophagy substrate degradation, so as to regulate autophagy, so as to promote the clearance of Aβ1-42 to improve SAMP8 memory impairment in mice.
Yishen Huazhuo Decoction induces autophagy to promote the clearance of Aβ1-42 in SAMP8 mice: mechanism research of a traditional Chinese formula against Alzheimer’s disease
White Matter Brain Research Network in Alzheimer’s Disease Using Persistent Features
Despite the severe social burden caused by Alzheimer’s disease (AD), there is no drug on the can change the progression of the disease have been identified yet. Structural brain tissue research provides an opportunity to understand the physiological damage caused by AD and its precursor, mild cognitive impairment (MCI). More recently, persistent homology has been used to study the brain network dynamics and characteristics of the global network organization.
However, it is not clear how these parameters reflect structural changes in the brain tissue of patients with AD or MCI. In this study, we proposed earlier persistent features and various measures traditionally used graph theory to measure the topological properties of white matter (WM) network in 150 subjects with diffusion tensor imaging (DTI). We found no significant difference in these measures between AD, MCI and normal controls (NC) under different brain partitioning scheme.
Description: Human frontal lobe tissue lysate was prepared by homogenization using a proprietary technique. The tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The human frontal lobe tissue total protein is provided in a buffer including HEPES (pH7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, Sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the frontal lobe tissue pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The frontal lobe tissue is then Western analyzed by either GAPDH or β-actin antibody, and the expression level is consistent with each lot.
Frozen Tissue Section - Human Adult Normal: Brain: Frontal Lobe
Description: Human parietal lobe tissue lysate was prepared by homogenization using a proprietary technique. The tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The human parietal lobe tissue total protein is provided in a buffer including HEPES (pH7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, Sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the parietal lobe tissue pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The parietal lobe tissue is then Western analyzed by either GAPDH or β-actin antibody, and the expression level is consistent with each lot.
Description: Human temporal lobe tissue lysate was prepared by homogenization using a proprietary technique. The tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The human temporal lobe tissue total protein is provided in a buffer including HEPES (pH7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, Sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the temporal lobe tissue pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The temporal lobe tissue is then Western analyzed by either GAPDH or β-actin antibody, and the expression level is consistent with each lot.
Genomic DNA - Parkinson's Disease: Brain: Frontal Lobe, from a single donor
Description: Human occipital lobe tissue lysate was prepared by homogenization using a proprietary technique. The tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The human occipital lobe tissue total protein is provided in a buffer including HEPES (pH7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, Sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the occipital lobe tissue pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The occipital lobe tissue is then Western analyzed by either GAPDH or β-actin antibody, and the expression level is consistent with each lot.
Genomic DNA - Alzheimer's Disease: Brain, from a single donor
Description: Human brain temporal lobe tissue membrane protein lysate was prepared by isolating the membrane protein from whole tissue homogenates using a proprietary technique. The human temporal lobe tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The membrane protein is provided in a buffer including HEPES (pH 7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the isolated brain temporal lobe tissue membrane protein pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The isolated brain temporal lobe tissue membrane protein is then Western analyzed by either GAPDH or β-actin antibody to confirm there is no signal or very weak signal.
network integration decreased and increased network separation expressed in AD and MCI. In addition, measures of persistent homology-based show statistically stronger capability and durability of the actions graph-traditional theory, suggesting that they represent a more sensitive approach to detect structural brain changes and to better understand AD symptomology at the network level. These findings contribute to an increased understanding of the structural connectome in AD and provide a new approach to potentially track the development of AD.