scholarly journals Quantitative Proteomics Reveal the Protective Effects of the Combined Chinese Herbal Extracts Against Alzheimer's Disease via Modulating the Expression of Synapse-associated Proteins in Mouse Model

2021 ◽  
Author(s):  
Qianqian Huang ◽  
Haibin Zhao ◽  
Chen Zhang ◽  
Ying Hao ◽  
Qihong Ma ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mouse Model ◽  
Quantitative Proteomics ◽  
Neuronal Apoptosis ◽  
Protective Efficacy ◽  
Chinese Herbs ◽  
Binding Potential ◽  
Chemical Components ◽  
Glutamatergic Synapse ◽  
Age Related

Abstract BackgroundAlzheimer's Disease (AD) as an age-related, irreversible neurodegenerative disease, characterized by cognitive dysfunction, has become progressively serious as a result of a global increase in life expectancy. As more mechanism of AD were discovered, therapeutic strategies using traditional Chinese medicine are under investigation for AD treatment, with efforts to improve efficacy and clarify the mechanism. Gastrodia, elata Blume, Polygala tenuifolia Willd., Cistanche deserticola Ma, Rehmannia lutinosa (Gaertn.)DC.,Acorus gramineus Aiton, and Curcuma longa L. are well-known chinese herbs with neuroprotective effects and widely used as a combination in traditional Chinese decoction for AD treatment. The purpose of this study was to investigate the synergistic protective efficacy of the combination (composed of extracts from these six Chinese medicines, CuraUltra), and the protein targets on scopolamine-induced cognitive impairment, using the proteomics analysis.MethodsScopolamine-induced cognitive impairment mouse model was established. Behavioral tests, Nissl Staining, cerebral cholinergic system alterations and neuronal apoptosis characteristics were examined to evaluate the ameliorating effects of CuraUltra on cognitive impairment induced by scopolamine. To identify the potential molecular mechanism responsible for the effect on CuraUltra treatment, label-free quantitative proteomics by tandem mass spectrometry (LC-MS/MS) were performed. Critical altered proteins were validated by qPCR and Western blotting. Molecular docking was finally performed to evaluate the binding potential of chemical components with the target proteins.Results Administration of CuraUltra significantly recovered scopolamine-induced cognitive impairment, as evidenced by the improved learning and memory ability, reduced pathological damage of hippocampus, increased content of Ach, decreased activity of AchE, and ameliorated expression levels of the neuronal apoptosis-related protein in the hippocampus of mice. Using quantitative proteomics technology, we observed 252 differentially expressed proteins. Compared with the model group, after CuraUltra treatments, a remarkedly alteration in PPP3CC, PKA, P38MAPK, RASA4, DNAJB1, SNAPIN was also observed. Notably, several significant proteins are in the glutamatergic synapse signaling pathway. Moreover, we confirmed that the PPP3CC appears to decreased as the AD pathological development, and may be positively correlated with the phosphorylation level of PKA, thereby inhibiting the activation of P38MAPK phosphorylation.ConclusionsAdministration of CuraUltra was effective on alleviating scopolamine-induced cognitive impairment, which might be through modulation of glutamatergic synapse. Consequently, our quantitative proteome data obtained from scopolamine-treated model mice successfully characterized AD-related biological alterations and proposed novel protein biomarkers for AD.

scholarly journals Age-related cognitive impairment is associated with long-term neuroinflammation and oxidative stress in a mouse model of episodic systemic inflammation

2018 ◽  
Vol 15 (1) ◽  
Author(s):  
Joana Costa d’Avila ◽  
Luciana Domett Siqueira ◽  
Aurélien Mazeraud ◽  
Estefania Pereira Azevedo ◽  
Debora Foguel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Systemic Inflammation ◽  
Age Related ◽  
And Oxidative Stress

scholarly journals Krill Oil Attenuates Cognitive Impairment by the Regulation of Oxidative Stress and Neuronal Apoptosis in an Amyloid β-Induced Alzheimer’s Disease Mouse Model

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3942
Author(s):  
Ji Hyun Kim ◽  
Hui Wen Meng ◽  
Mei Tong He ◽  
Ji Myung Choi ◽  
Dongjun Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Neuronal Apoptosis ◽  
Morris Water Maze Test ◽  
Krill Oil ◽  
Cognitive Improvement ◽  
The Brain

In the present study, we investigated the cognitive improvement effects and its mechanisms of krill oil (KO) in Aβ25–35-induced Alzheimer’s disease (AD) mouse model. The Aβ25–35-injected AD mouse showed memory and cognitive impairment in the behavior tests. However, the administration of KO improved novel object recognition ability and passive avoidance ability compared with Aβ25–35-injected control mice in behavior tests. In addition, KO-administered mice showed shorter latency to find the hidden platform in a Morris water maze test, indicating that KO improved learning and memory abilities. To evaluate the cognitive improvement mechanisms of KO, we measured the oxidative stress-related biomarkers and apoptosis-related protein expressions in the brain. The administration of KO inhibited oxidative stress-related biomarkers such as reactive oxygen species, malondialdehyde, and nitric oxide compared with AD control mice induced by Aβ25–35. In addition, KO-administered mice showed down-regulation of Bax/Bcl-2 ratio in the brain. Therefore, this study indicated that KO-administered mice improved cognitive function against Aβ25–35 by attenuations of neuronal oxidative stress and neuronal apoptosis. It suggests that KO might be a potential agent for prevention and treatment of AD.

Resolving and Rescuing Developmental Miswiring in a Mouse Model of Cognitive Impairment

2019 ◽  
Author(s):  
Mattia Chini ◽  
Jastyn A. Pöpplau ◽  
Christoph Lindemann ◽  
Laura Carol-Perdiguer ◽  
Marilena Hnida ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mouse Model

Elevated Inflammatory Markers and Arterial Stiffening Exacerbate Tau but Not Amyloid Pathology in Older Adults with Mild Cognitive Impairment

2021 ◽  
pp. 1-13
Author(s):  
Alexandra L. Clark ◽  
Alexandra J. Weigand ◽  
Kelsey R. Thomas ◽  
Seraphina K. Solders ◽  
Lisa Delano-Wood ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Inflammatory Markers ◽  
Memory Performance ◽  
Cognitive Testing ◽  
Interactive Effects ◽  
Protein Biomarkers ◽  
Age Related ◽  
T Tau

Background: Age-related cerebrovascular and neuroinflammatory processes have been independently identified as key mechanisms of Alzheimer’s disease (AD), although their interactive effects have yet to be fully examined. Objective: The current study examined 1) the influence of pulse pressure (PP) and inflammatory markers on AD protein levels and 2) links between protein biomarkers and cognitive function in older adults with and without mild cognitive impairment (MCI). Methods: This study included 218 ADNI (81 cognitively normal [CN], 137 MCI) participants who underwent lumbar punctures, apolipoprotein E (APOE) genotyping, and cognitive testing. Cerebrospinal (CSF) levels of eight pro-inflammatory markers were used to create an inflammation composite, and amyloid-beta 1–42 (Aβ 42), phosphorylated tau (p-tau), and total tau (t-tau) were quantified. Results: Multiple regression analyses controlling for age, education, and APOE ɛ4 genotype revealed significant PP x inflammation interactions for t-tau (B = 0.88, p = 0.01) and p-tau (B = 0.84, p = 0.02); higher inflammation was associated with higher levels of tau within the MCI group. However, within the CN group, analyses revealed a significant PP x inflammation interaction for Aβ 42 (B = –1.01, p = 0.02); greater inflammation was associated with higher levels of Aβ 42 (indicative of lower cerebral amyloid burden) in those with lower PP. Finally, higher levels of tau were associated with poorer memory performance within the MCI group only (p s <  0.05). Conclusion: PP and inflammation exert differential effects on AD CSF proteins and provide evidence that vascular risk is associated with greater AD pathology across our sample of CN and MCI older adults.

scholarly journals A Preliminary Analysis of Hearing Loss and Its Association With Mild Cognitive Impairment

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 451-452
Author(s):  
Mary Caroline Yuk ◽  
Rebecca Allen ◽  
Marcia Hay-McCutcheon ◽  
Dana Carroll ◽  
Anne Halli-Tierney
Keyword(s):  
Hearing Loss ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Emotional Health ◽  
Medical Center ◽  
Pearson Correlation ◽  
Well Being ◽  
Hearing Screening ◽  
Community Dwelling ◽  
Age Related

Abstract Age related hearing loss, or presbycusis, is a global condition that is increasing in its prevalence. Despite being one of the most common chronic conditions among the older population, there is much more to understand about its association with other aspects of physical and emotional health and well-being. Current research is suggesting that hearing loss is more prevalent in those with cognitive impairment compared to those without cognitive impairment. This study analyzed the incidence of hearing loss and its linkage to mild cognitive impairment in a community-dwelling geriatric population. With the increasing prevalence of this condition in both rural and urban communities of Alabama, it becomes a more pressing matter to understand comorbidities and risk factors for future decline in functioning. This study was conducted in an interdisciplinary geriatrics primary care outpatient clinic in a Family, Internal, and Rural Medicine department affiliated with a university medical center in the Deep South. Ninety-one participants completed the Montreal Cognitive Assessment (MoCA) and a hearing screening. Hearing screenings were conducted in quiet rooms in the medical center using Phonak hearing screening cards. Detection of 500, 1000, 2000, and 4000 Hz tones was assessed. Pearson correlation analyses demonstrated an association between hearing loss mild cognitive impairment. Poorer hearing was significantly associated with lower scores on the MoCA. Conducting behavioral health screenings like this in other primary geriatrics clinics and community settings could improve care and identification of patient needs by integrating important data regarding comorbidities and independent living.

scholarly journals Cellular Werner Phenotypes in Mice Expressing a Putative Dominant-Negative Human WRN Gene

Genetics ◽  
2000 ◽  
Vol 154 (1) ◽  
pp. 357-362
Author(s):  
Lan Wang ◽  
Charles E Ogburn ◽  
Carol B Ware ◽  
Warren C Ladiges ◽  
Hagop Youssoufian ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mice ◽  
Werner Syndrome ◽  
Dominant Negative ◽  
Dominant Negative Mutation ◽  
Fibroblast Cultures ◽  
Age Related

Abstract Mutations at the Werner helicase locus (WRN) are responsible for the Werner syndrome (WS). WS patients prematurely develop an aged appearance and various age-related disorders. We have generated transgenic mice expressing human WRN with a putative dominant-negative mutation (K577M-WRN). Primary tail fibroblast cultures from K577M-WRN mice showed three characteristics of WS cells: hypersensitivity to 4-nitroquinoline-1-oxide (4NQO), reduced replicative potential, and reduced expression of the endogenous WRN protein. These data suggest that K577M-WRN mice may provide a novel mouse model for the WS.

scholarly journals Impaired spike-gamma coupling of area CA3 fast-spiking interneurons as the earliest functional impairment in the AppNL-G-F mouse model of Alzheimer’s disease

2021 ◽  
Author(s):  
Luis Enrique Arroyo-García ◽  
Arturo G. Isla ◽  
Yuniesky Andrade-Talavera ◽  
Hugo Balleza-Tapia ◽  
Raúl Loera-Valencia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Functional Impairment ◽  
Amyloid Β ◽  
Gamma Oscillations ◽  
Gamma Oscillation ◽  
Gamma Rhythm ◽  
Fast Spiking

AbstractIn Alzheimer’s disease (AD) the accumulation of amyloid-β (Aβ) correlates with degradation of cognition-relevant gamma oscillations. The gamma rhythm relies on proper neuronal spike-gamma coupling, specifically of fast-spiking interneurons (FSN). Here we tested the hypothesis that decrease in gamma power and FSN synchrony precede amyloid plaque deposition and cognitive impairment in AppNL-G-F knock-in mice (AppNL-G-F). The aim of the study was to evaluate the amyloidogenic pathology progression in the novel AppNL-G-F mouse model using in vitro electrophysiological network analysis. Using patch clamp of FSNs and pyramidal cells (PCs) with simultaneous gamma oscillation recordings, we compared the activity of the hippocampal network of wild-type mice (WT) and the AppNL-G-F mice at four disease stages (1, 2, 4, and 6 months of age). We found a severe degradation of gamma oscillation power that is independent of, and precedes Aβ plaque formation, and the cognitive impairment reported previously in this animal model. The degradation correlates with increased Aβ1-42 concentration in the brain. Analysis on the cellular level showed an impaired spike-gamma coupling of FSN from 2 months of age that correlates with the degradation of gamma oscillations. From 6 months of age PC firing becomes desynchronized also, correlating with reports in the literature of robust Aβ plaque pathology and cognitive impairment in the AppNL-G-F mice. This study provides evidence that impaired FSN spike-gamma coupling is one of the earliest functional impairment caused by the amyloidogenic pathology progression likely is the main cause for the degradation of gamma oscillations and consequent cognitive impairment. Our data suggests that therapeutic approaches should be aimed at restoring normal FSN spike-gamma coupling and not just removal of Aβ.

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