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

2020 ◽  
Vol 19 (4) ◽  
pp. 276-289
Author(s):  
Kai Wang ◽  
Weiming Sun ◽  
Jiachun Xu ◽  
Qijing Qin ◽  
Zhen Yu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Learning And Memory ◽  
Neuronal Loss ◽  
Tunel Staining ◽  
Initiation Increase ◽  
Apoptosis Index ◽  
Significant Difference ◽  
Related Proteins ◽  
Samp8 Mice

Background: Studies have found that autophagy could promote the clearance of Aβ. To promote and maintain the occurrence of autophagy in Alzheimer's disease (AD) might be a potential way to reduce neuronal loss and improve the learning and memory of AD. Objective: To investigate the possible mechanisms of Yishen Huazhuo Decoction (YHD) against AD model. Methods: Forty 7-month-old male SAMP8 mice were randomly divided into model (P8) group and YHD group, 20 in each group, with 20 SAMR1 mice as control (R1) group. All mice were intragastrically administered for 4 weeks, YHD at the dosage of 6.24g/kg for YHD group, and distilled water for P8 group and R1 group. Morris water maze (MWM) test, Nissl’s staining, TEM, TUNEL staining, immunofluorescence double staining, and western blot analysis were applied to learning and memory, structure and ultrastructure of neurons, autophagosome, apoptosis index, Aβ, LAMP1, and autophagy related proteins. Results: The escape latency time of YHD group was significantly shorter on the 4th and 5th day during MWM test than those in 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’s staining showed that the number of neurons in YHD group increased significantly (P<0.0001). TEM showed in YHD group, the nucleus of neurons was slightly irregular, with slightly reduced organelles, partially fused and blurred cristae and membrane of mitochondria. The apoptosis index of YHD group showed a decreasing trend, without statistically significant difference (P=0.093>0.05), while Caspase3 expression in YHD group was significantly lower (P=0.044<0.05). YHD could promote the clearance of Aβ1-42 protein, improve the expression of Beclin-1 and p-Bcl2 proteins, reduce mTOR and p62 proteins. Conclusions: YHD could induce autophagy initiation, increase the formation of autophagosomes and autolysosome, promote the degradation of autophagy substrates, thereby to regulate autophagy, thereby to promote the clearance of Aβ1-42 to improve memory impairment in SAMP8 mice.

scholarly journals Adequacy of food consumption in elderly Alzheimer’s disease in a community of Southern Brazil: a Cross-sectional study

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 671
Author(s):  
Glaucia Renee Hilgemberg ◽  
Aline Jacoski de Oliveira Krüger da Silva ◽  
Bárbara Luisa Fermino ◽  
Camila Diedrich ◽  
Simone Carla Benincá ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nutritional Status ◽  
Neuronal Loss ◽  
Great Difficulty ◽  
Amyloid Peptide ◽  
Control Group ◽  
Food Record ◽  
Cross Sectional ◽  
Significant Difference

Background: Alzheimer's disease (AD) is the most common cause of dementia, with a multifactorial etiology, in which the person has great difficulty identifying feelings of hunger, satiety, and feeding, which may affect their nutritional status. Pathologically, it is associated with neurodegeneration of synapses followed by neuronal loss, accompanied by glial proliferation surrounded by neurofibrillary tangles, beta-amyloid peptide (Aβ) deposition, inflammation and cerebrovascular injury hindering the ability to perform activities of daily living. This study aimed to analyze quantitatively the differences between an elderly group with AD and a control group, in terms of macro and micronutrient consumption evaluation. Methods: the study involved 69 participants who were assessed via collection of anthropometric measurements (weight, height and body mass index) with nutritional status being assessed by 24-hour food recall and three-day food record. Cognitive assessments were performed using the Mini-Mental State Examination (MMSE) and Clinical Dementia Ranting (CDR). Results: The intake of lipids in patients with severe dementia, was lower (p <0.05). The consumption of proteins showed a decrease with demential advance. For vitamins, there was a significant difference (p <0.05) in the amount of thiamine, niacin, vitamin D, E and K and calcium, chromium and iodine minerals, which were significantly reduced in AD patients (p <0.05). Conclusions: Decreases in macronutrient and micronutrient consumption may result in a consequent impairment of nutritional status, dementia progression, and decreased quality and life expectancy of elderly patients with AD.

scholarly journals Neurokinin 3 Receptor Effects on Cognitive Behaviour in a Rat Model of Alzheimer's Disease

2021 ◽  
Author(s):  
Raviye Ozen Koca ◽  
Zulfikare Isik Solak Gormus ◽  
Hatice Solak ◽  
Aynur Koc ◽  
İbrahim Kılınç ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Learning And Memory ◽  
Albino Rats ◽  
Cholinergic Mechanisms ◽  
Positive Effects ◽  
Information Hypothesis ◽  
Cognitive Behaviour ◽  
Significant Difference ◽  
Neurokinin 3 Receptor

Abstract Alzheimer's disease (AD) is accepted as a form of progressive and irreversible dementia. It is known that cholinergic systems are commonly affected in AD. Neurokinin 3 receptor (NK3R) is involved in learning and memory related processes. Activation of NK3R is known to facilitate the release of many neurotransmitters such as acetylcholine (Ach), dopamine (DA), noradrenaline (NA). Based on this information, hypothesis of the study that NK3R agonism can have positive effects on behavioral and learning parameters through cholinergic and catecholaminergic mechanisms. The aim of this study was to investigate the effects of NK3R agonist senktide on cognitive and neurobehavioral mechanisms in model of AD.50 adult male Wistar albino rats were obtained; Control, AD, Control+NK3R agonist, AD+NK3R agonist, AD+NK3R agonist+antagonist groups. AD model was established by administering Aβ1-42 intracerebroventricularly. Following NK3R agonist+antagonist injections, open field (OF) and Morris water maze (MWM) were applied for behavioral and learning parameters. Hippocampus and cortex tissues were extracted. Analysis of cholinergic mechanisms from these tissues were performed by ELISA method.Group-time effect was significant in OF (p<0.05). Distance moved parameter was significant between groups in MWM (p<0.05). There was a significant difference between groups in AChE and ChAT levels (p<0.05). DA concentrations of brainstem samples were significant (p<0.05). There was no significant difference in NA concentration (p>0.05). NK3R agonists were found to be effective in improving cognitive functions in rats with AD pathology. It has been observed that positive effects on learning and memory performances can be mediated by cholinergic mechanisms.

scholarly journals Electroacupuncture could balance the gut microbiota and improve the learning and memory abilities of Alzheimer’s disease animal model

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259530
Author(s):  
Jing Jiang ◽  
Hao Liu ◽  
Zidong Wang ◽  
Huiling Tian ◽  
Shun Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Gut Microbiota ◽  
Learning And Memory ◽  
Amplicon Sequencing ◽  
Tnf Α ◽  
16S Rdna Amplicon Sequencing ◽  
Nerve System ◽  
Samp8 Mice

Alzheimer’s disease (AD), as one of most common dementia, mainly affects older people from the worldwide. In this study, we intended to explore the possible mechanism of improving cognitive function and protecting the neuron effect by electroacupuncture. Method: We applied senescence-accelerated mouse prone 8 (SAMP8) mice as AD animal model, used Morris water maze, HE staining, 16S rDNA amplicon sequencing of gut microbiota and ELISA to demonstrate our hypothesis. Results: electroacupuncture improved the learning and memory abilities in SAMP8 mice (P<0.05) and could protect the frontal lobe cortex and hippocampus of SAMP8 mice; electroacupuncture significantly decreased the expression of IL-1β (P<0.01), IL-6 (P<0.01) and TNF-α (P<0.01 in hippocampus, P<0.05 in serum) in serum and hippocampus; electroacupuncture balanced the quantity and composition of gut microbiome, especially of the relative abundance in Delta-proteobacteria (P<0.05) and Epsilon-proteobacteria (P<0.05). Conclusion: electroacupuncture treatment could inhibit the peripheral and central nerve system inflammatory response by balancing the gut microbiota.

Entorhinal verrucae correlate with surface geometry

2012 ◽  
Vol 3 (2) ◽  
Author(s):  
Jean Augustinack ◽  
Kristen Huber ◽  
Gheorghe Postelnicu ◽  
Matthew Frosch ◽  
Rudolph Pienaar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Entorhinal Cortex ◽  
Ex Vivo ◽  
Neurofibrillary Tangle ◽  
Neuronal Loss ◽  
Surface Geometry ◽  
Curvature Analysis ◽  
Significant Difference ◽  
Large Neurons

AbstractEntorhinal verrucae are unique, small elevations on the surface of entorhinal cortex, formed due to distinctive clustering of large neurons in entorhinal layer II. In Alzheimer’s disease, the verrucae atrophy as a result of neurofibrillary tangle formation and concomitant neuronal loss. Previously, we found significant decreases in verrucae height, width, surface area, and volume even in the mildest stage of Alzheimer’s disease. In this report, we introduce a new method for analyzing verrucae prominence using measures of their curvature. Smoothed surfaces and curvatures were generated using FreeSurfer (http://surfer.nmr.mgh.harvard.edu) from 100 μm3 ex vivo MRI isosurfaces. We examined the positive and negative components of mean curvature AreaNorm(H+/-) and Gaussian curvature AreaNorm(K +/−) in entorhinal cortex. A significant difference was found between entorhinal (n=10) and non-entorhinal cortices (n=9) for both AreaNorm(H+/-) and AreaNorm(K +/−). We also validated our curvature analysis through a comparison with previously published verrucae measures derived from manual labels of individual verrucae. A significant positive correlation was found between mean verrucae height and AreaNorm(H+/-). Both mean verrucae height and volume were significantly positively correlated with AreaNorm(K +/−). These results demonstrate that K and H are accurate metrics for detecting the presence or absence of entorhinal verrucae. Curvature analysis may be a useful and sensitive technique for detecting local surface changes in entorhinal cortex.

scholarly journals Fumanjian, a Classic Chinese Herbal Formula, Can Ameliorate the Impairment of Spatial Learning and Memory through Apoptotic Signaling Pathway in the Hippocampus of Rats withAβ1–40-Induced Alzheimer’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Hai-yan Hu ◽  
Zhi-hui Cui ◽  
Hui-qin Li ◽  
Yi-ru Wang ◽  
Xiang Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Learning And Memory ◽  
Ming Dynasty ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Tunel Staining ◽  
Apoptotic Signaling ◽  
Chinese Herbal

Alzheimer’s disease (AD) is the most common form of dementia and lacks disease-altering treatments. Fumanjian (FMJ), a famous classic Chinese herbal prescription for dementia, was first recorded in theComplete Works of Jingyueduring the Ming Dynasty. This study aimed to investigate whether FMJ could prevent cognitive deficit and take neuroprotective effects inAβ1–40-induced rat model through apoptotic signaling pathway. AD model was established by bilateral injection ofAβ1–40into hippocampus in rat. All rats were tested for their capabilities of spatial navigation and memorization by Morris water maze. Apoptosis was tested using TUNEL staining in hippocampus neuronal cells; RT-PCR tested expression of Bcl-2 and Bax mRNA; western blotting tested protein level of cleaved caspase-3. After 14 days of treatment, FMJ significantly improved the escape latency and enhanced platform-cross number compared with theAβ1–40-injected group (P<0.05orP<0.01). FMJ also significantly decreased number of TUNEL-positive neuronal apoptosis and the expressions of Bax and cleaved Caspase-3 and increased the expression of Bcl-2 (P<0.01) compared with AD model group. In conclusion, FMJ exerts a protective effect againstAβ1–40-induced learning and memory deficits and neuronal apoptosis, suggesting that FMJ could be used as a potential therapeutic formula for AD.

scholarly journals Cornel iridoid glycoside ameliorated Alzheimer's disease-like pathologies and necroptosis through RIPK1/MLKL pathway in young and aged SAMP8 mice

2021 ◽  
Author(s):  
Denglei Ma ◽  
Yanzheng Li ◽  
Yanqiu Zhu ◽  
Weipeng Wei ◽  
Li Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Brain Aging ◽  
Neuronal Loss ◽  
Iridoid Glycoside ◽  
Intragastric Administration ◽  
Cornel Iridoid Glycoside ◽  
Samp8 Mice ◽  
The Brain

Abstract Background Aging is an important risk factor for sporadic Alzheimer’s disease (AD) and other neurodegenerative diseases. Senescence-accelerated mouse-prone 8 (SAMP8) is used as an animal model for brain aging and sporadic AD researches. The aim of the current study was to investigate the pharmacological effects of cornel iridoid glycoside (CIG), an active ingredient of Cornus officinalis, on AD-type pathological changes in young and aged SAMP8 mice. Methods Nissl and immunohistochemical staining was applied to detect NeuN-labeled neurons and myelin basic protein-labeled myelin sheath,. Western blotting was used to detect the expression levels of related proteins of synapse, APP processing and necroptosis. Results The results showed that SAMP8 mice at the age of 6 and 14 months exhibited age-related neuronal loss, demyelination, synaptic damage, and APP amyloidogenic processing. In addition, the increased levels of receptor-interacting protein kinase-1 (RIPK1), mixed lineage kinase domain-like protein (MLKL) and p-MLKL indicating necroptosis were found in the brain of SAMP8 mice. Intragastric administration of CIG for 2 months alleviated neuronal loss and demyelination, increased the expression of synaptophysin, postsynaptic density protein 95 and AMPA receptor subunit 1, elevated the levels of soluble APPα fragment and a disintegrin and metalloproteinase 10 (ADAM10), and decreased the levels of RIPK1, p-MLKL and MLKL in the brain of young and aged SAMP8 mice. Conclusion This study denoted that CIG might be a potential drug for aging-associated neurodegenerative diseases such as AD.

scholarly journals Therapy of Dredging the Bowels Enhanced the Neuroprotective Effect of Nourishing Kidney Herbs on Hippocampal Cholinergic System in Alzheimer’s Disease Model Rat Induced by Aβ 1-42

2018 ◽  
Vol 2018 ◽  
pp. 1-12
Author(s):  
Lu-Da Feng ◽  
Yang Tian ◽  
Xin Wang ◽  
Run Dai ◽  
Song Cai ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Learning And Memory ◽  
Cholinergic System ◽  
Neuroprotective Effect ◽  
Disease Model ◽  
Memory Deficits ◽  
Underlying Mechanism ◽  
Chat Activity ◽  
Significant Difference

Background. Therapy of nourishing kidney has been used for treating memory deficits of Alzheimer’s disease (AD) for thousands of years based on traditional Chinese medicine. However, we found the therapy of dredging the bowels could alleviate both memory deficits and mental symptoms of AD in clinic. Objective. To determine whether the therapy of dredging the bowels could enhance the neuroprotective effect of nourishing kidney herbs for treating AD rats, and to explore the underlying mechanism of the combination of nourishing kidney and dredging the bowels (NKDB) herbs. Methods. 60 rats were randomly divided into sham-operated group (SOG), model group (MG), nourishing kidney group (NKG), dredging the bowels group (DBG), nourishing kidney and dredging the bowels group (NKDBG), and donepezil hydrochloride group (DHG). The model establishment was performed by injecting Aβ 1-42 into the hippocampal CA1 region. Animals received aqueous solution of Chinese herbal medicine or western medicine while SOG received only distilled water. Ability of learning and memory were assessed by Morris water maze. Acetylcholinesterase(AChE) and choline acetyltransferase (ChAT) activity and positive cells in the hippocampus were detected by the biochemical and immunofluorescent assay. Results. All rats were in the same baseline. While after model establishment, ability of learning and memory of MG, NKG, DBG, NKDBG, and DHG were significantly impaired compared with SOG. Whereas after treatment, ability of learning and memory of NKG, DBG, NKDBG, and DHG were significantly improved compared with MG. Additionally, AChE activity of NKG, DBG, and NKDBG was significantly decreased, meanwhile ChAT activity showed an increased tendency. The number of AChE-positive cells and ChAT-positive cells of both NKDBG and DHG were significantly decreased and increased respectively, superior to those when compared with NKG and DBG. What’s more, there was no significant difference between NKDBG and DHG. Conclusion. Therapy of dredging the bowels could enhance the neuroprotective effect of nourishing kidney herbs by reversing morphological damage of hippocampal cholinergic system. Furthermore, treatment with NKDB herbs could be effectively against AD, providing a practical therapeutic strategy in clinic.

scholarly journals P2-021: METFORMIN AND TOPIRAMATE IMPROVE LEARNING AND MEMORY IN DIABETIC MICE AND SAMP8 MICE MODEL OF ALZHEIMER'S DISEASE

2014 ◽  
Vol 10 ◽  
pp. P477-P478 ◽  
Author(s):  
John Edward Morley ◽  
Michael L. Niehoff ◽  
Michael W. Bergin ◽  
Elizabeth C. Roesler ◽  
Gul N. Shah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Learning And Memory ◽  
Diabetic Mice ◽  
Mice Model ◽  
Model Of Alzheimer’S Disease ◽  
Samp8 Mice

scholarly journals Cornel Iridoid Glycoside Ameliorated Alzheimer’s Disease-Like Pathologies and Necroptosis through RIPK1/MLKL Pathway in Young and Aged SAMP8 Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Denglei Ma ◽  
Yanzheng Li ◽  
Yanqiu Zhu ◽  
Weipeng Wei ◽  
Li Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Locomotor Activity ◽  
Neurodegenerative Diseases ◽  
Neuronal Loss ◽  
Iridoid Glycoside ◽  
Intragastric Administration ◽  
Cornel Iridoid Glycoside ◽  
Samp8 Mice ◽  
The Brain

Background. Aging is an important risk factor for sporadic Alzheimer’s disease (AD) and other neurodegenerative diseases. Senescence-accelerated mouse-prone 8 (SAMP8) is used as an animal model for brain aging and sporadic AD research studies. The aim of the current study was to investigate the pharmacological effects of cornel iridoid glycoside (CIG), an active ingredient of Cornus officinalis, on AD-type pathological changes in young and aged SAMP8 mice. Methods. Locomotor activity test was used to detect the aging process of SAMP8 mice. Nissl staining and immunohistochemical staining were applied to detect neurons and myelin basic protein-labelled myelin sheath. Western blotting was used to detect the expression levels of related proteins of synapse, APP processing, and necroptosis. Results. The results showed that SAMP8 mice at the age of 6 and 14 months exhibited lower locomotor activity, age-related neuronal loss, demyelination, synaptic damage, and APP amyloidogenic processing. In addition, the increased levels of receptor-interacting protein kinase-1 (RIPK1), mixed lineage kinase domain-like protein (MLKL), and p-MLKL indicating necroptosis were found in the brain of SAMP8 mice. Intragastric administration of CIG for 2 months improved locomotor activity; alleviated neuronal loss and demyelination; increased the expression of synaptophysin, postsynaptic density protein 95, and AMPA receptor subunit 1; elevated the levels of soluble APPα fragment and disintegrin and metalloproteinase 10 (ADAM10); and decreased the levels of RIPK1, p-MLKL, and MLKL in the brain of young and aged SAMP8 mice. Conclusion. This study denoted that CIG might be a potential drug for aging-related neurodegenerative diseases such as AD.

scholarly journals Tau-induced focal neurotoxicity and network disruption related to apathy in Alzheimer’s disease

2018 ◽  
Vol 89 (11) ◽  
pp. 1208-1214 ◽  
Author(s):  
Soichiro Kitamura ◽  
Hitoshi Shimada ◽  
Fumitoshi Niwa ◽  
Hironobu Endo ◽  
Hitoshi Shinotoh ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Diffusion Tensor ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
Brain Regions ◽  
Subsequent Decrease ◽  
Positron Emission ◽  
Significant Difference ◽  
Network Disruption

ObjectiveApathy is a common neuropsychological symptom in Alzheimer’s disease (AD), and previous studies demonstrated that neuronal loss and network disruption in some brain regions play pivotal roles in the pathogenesis of apathy. However, contributions of tau and amyloid-β (Aβ) depositions, pathological hallmarks of AD, to the manifestation of apathy remain elusive.MethodsSeventeen patients with AD underwent positron emission tomography (PET) with11C-pyridinyl-butadienyl-benzothiazole 3 (11C-PBB3) and11C-Pittsburgh compound-B (11C-PiB) to estimate tau and Aβ accumulations using standardised uptake value ratio (SUVR) images.11C-PBB3 and11C-PiB SUVR were compared between AD patients with high and low Apathy Scale (AS) scores. Additionally, volumetric and diffusion tensor MRI was performed in those areas where any significant difference was observed in PET analyses. Correlation and path analyses among AS and estimated imaging parameters were also conducted.ResultsAD patients with high AS scores showed higher11C-PBB3 SUVR in the orbitofrontal cortex (OFC) than those with low AS scores, while11C-PiB SUVR in any brain regions did not differ between them. Elevated11C-PBB3 SUVR in OFC, decreased OFC thickness and decreased fractional anisotropy (FA) in the uncinate fasciculus (UNC), which is structurally connected to OFC, correlated significantly with increased scores of the AS. Path analysis indicated that increased11C-PBB3 SUVR in OFC affects apathy directly and through reduction of OFC thickness and subsequent decrease of FA in UNC.ConclusionsThe present findings suggested that tau pathology in OFC may provoke focal neurotoxicity in OFC and the following disruption of the OFC-UNC network, leading to the emergence and progression of apathy in AD.

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