scholarly journals Correction: Neuroprotective effects of bajijiasu against cognitive impairment induced by amyloid-β in APP/PS1 mice

Oncotarget ◽  
2018 ◽  
Vol 9 (39) ◽  
pp. 25750-25750 ◽  
Author(s):  
Haobin Cai ◽  
Yijie Wang ◽  
Jiayang He ◽  
Tiantian Cai ◽  
Jun Wu ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Amyloid Β ◽  
Neuroprotective Effects

scholarly journals Neuroprotective effects of bajijiasu against cognitive impairment induced by amyloid-β in APP/PS1 mice

Oncotarget ◽  
2017 ◽  
Vol 8 (54) ◽  
pp. 92621-92634 ◽  
Author(s):  
Haobin Cai ◽  
Yijie Wang ◽  
Jiayang He ◽  
Tiantian Cai ◽  
Jun Wu ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Amyloid Β ◽  
Neuroprotective Effects

Sophocarpine Attenuates Cognitive Impairment and Promotes Neurogenesis in a Mouse Model of Alzheimer’s Disease

2021 ◽  
pp. 1-12
Author(s):  
Jian-Ya Ye ◽  
Qingmao Hao ◽  
Yijun Zong ◽  
Yongqing Shen ◽  
Zhiqin Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Microglial Activation ◽  
Therapeutic Agent ◽  
Amyloid Β ◽  
Neuroprotective Effects ◽  
Model Of Alzheimer’S Disease ◽  
Inflammatory Processes ◽  
Inflammatory Changes

<b><i>Introduction:</i></b> Alzheimer’s disease (AD), which is characterized by abnormal deposition of amyloid-β (Aβ) plaques and impaired neurogenesis and cognition, still lacks an optimally effective therapeutic agent for its management, and mounting evidence has shown that inflammatory processes are implicated in AD. Sophocarpine has been reported to exert inflammation-regulating effects in various diseases. However, whether sophocarpine can exert anti-neuroinflammatory and neuroprotective effects in AD remains unclear. This study investigated whether sophocarpine could ameliorate the pathological features and potential mechanisms in a mouse AD model. <b><i>Methods:</i></b> APP/PS1 mice were treated with sophocarpine for 8 weeks. We quantified the effects of sophocarpine treatment on cognitive performance using a behavioral test. Brain Aβ deposits and neurogenesis were evaluated using immunofluorescence staining. We also assessed the morphology and inflammatory changes induced by sophocarpine administration and its expression in the hippocampus. <b><i>Results:</i></b> Administration of sophocarpine significantly alleviated cognitive impairment and reduced neural loss. APP/PS1 mice treated with sophocarpine showed reduced Aβ plaque deposits and enhanced neurogenesis. Sophocarpine markedly decreased the expression of inflammation markers and inhibited microglial activation. <b><i>Conclusions:</i></b> Sophocarpine could potentially alleviate cognitive impairment and brain damage in APP/PS1 mice with its neuroprotective effects via modulation of the inflammatory pathway.

Rifampicin Suppresses Amyloid-β Accumulation Through Enhancing Autophagy in the Hippocampus of a Lipopolysaccharide-Induced Mouse Model of Cognitive Decline

2020 ◽  
pp. 1-14
Author(s):  
Lihong Zhu ◽  
Qiongru Yuan ◽  
Zhaohao Zeng ◽  
Ruiyi Zhou ◽  
Rixin Luo ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mouse Model ◽  
Hippocampal Neurons ◽  
Cognitive Impairments ◽  
Amyloid Β ◽  
Underlying Mechanism ◽  
Autophagosome Formation ◽  
Neuroprotective Effects ◽  
Biochemical Assays ◽  
Cognitive Sequelae

Background: Alzheimer’s disease (AD) is characterized by amyloid-β (Aβ) deposition. The metabolism of Aβ is critically affected by autophagy. Although rifampicin is known to mediate neuroinflammation, the underlying mechanism by which rifampicin regulates the cognitive sequelae remains unknown. Objective: Based on our previous findings that rifampicin possesses neuroprotective effects on improving cognitive function after neuroinflammation, we aimed to examine in this study whether rifampicin can inhibit Aβ accumulation by enhancing autophagy in a mouse model of lipopolysaccharide (LPS)-induced cognitive impairment. Methods: Adult C57BL/6 mice were intraperitoneally injected with rifampicin, chloroquine, and/or LPS every day for 7 days. Pathological and biochemical assays and behavioral tests were performed to determine the therapeutic effect and mechanism of rifampicin on the hippocampus of LPS-induced mice. Results: We found that rifampicin ameliorated cognitive impairments in the LPS-induced mice. In addition, rifampicin attenuated the inhibition of autophagosome formation, suppressed the accumulation of Aβ1–42, and protected the hippocampal neurons against LPS-induced damage. Our results further demonstrated that rifampicin improved the neurological function by promoting autophagy through the inhibition of Akt/mTOR/p70S6K signaling pathway in the hippocampus of LPS-induced mice. Conclusion: Rifampicin ameliorates cognitive impairment by suppression of Aβ1–42 accumulation through inhibition of Akt/mTOR/p70S6K signaling and enhancement of autophagy in the hippocampus of LPS-induced mice.

Neuroprotective effects of nootkatone from Alpiniae oxyphyllae Fructus against amyloid-β-induced cognitive impairment

2017 ◽  
Vol 33 (1) ◽  
pp. 251-259 ◽  
Author(s):  
Bosai He ◽  
Fanxing Xu ◽  
Feng Xiao ◽  
Tingxu Yan ◽  
Bo Wu ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Amyloid Β ◽  
Neuroprotective Effects

Berberine nanoencapsulation attenuates hallmarks of scoplomine induced Alzheimer's-like disease in rats

2020 ◽  
Vol 15 ◽  
Author(s):  
Samar R. Saleh ◽  
Mariam M. Abady ◽  
Mohammed Nofal ◽  
Nashwa W. Yassa ◽  
Mohamed S. Abdel-latif ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Histopathological Examination ◽  
Memory Function ◽  
Amyloid Β ◽  
Active Pharmaceutical Ingredient ◽  
Isoquinoline Alkaloid ◽  
Drug Uptake ◽  
Male Rats ◽  
Morris Water Maze Test ◽  
Neuroprotective Effects

Background: Berberine (BBR), an isoquinoline alkaloid, acts as a multipotent active pharmaceutical ingredient to counteract several types of dementia based on its numerous pharmacological actions including antioxidant, antiinflammatory, cholesterol-lowering effect, and inhibition of Aβ production and AChE. However, BBR suffers from poor absorption, bioavailability and brain drug uptake. The present study is directed for the formulation and characterization of Chitosan BBR-nanoparticles (BBR-NPs) as well as the estimation of its neuroprotective effects against scopolamine induced cognitive impairments. Methods: BBR-NPs were formulated using ionic gelation method and tripolyphosphate was chosen as a cross linker. Nanoparticles size, zeta potential, encapsulation efficiency and releasing profile were estimated. To investigate the neuroprotective effects, adult fifty six Wistar male rats were randomly distributed into: three control groups, received saline, polyethylene glycol or chitosan- NPs respectively; induced group, received scopolamine (2 mg/ kg, i.p.) and three treated groups were orally administrated BBR (50 mg/ kg), BBR- NP (7 mg/ kg) and donepezil (2.25 mg/ kg, as positive control) followed by scopolamine injection after 40 min, daily for 4 weeks. Morris water maze test, oxidative stress parameters, cholinergic and amyloid-β processing intermediates as well as neuroplasticity markers and histopathological examination were assessed. Results: Our results showed that BBR- NPs were better than BBR and donepezil as BBR- NPs were powerful inhibitory ligands toward AChE and Aβ42 formation and significantly down regulated Tau, iNOS and BACE gene expression in rats’ hippocampus. BBR-NPs administration, at 1/6 of BBR therapeutic recommended dose, significantly improved learning and memory function. This could be accredited to the diminution of oxidative stress and amyloid-β toxicity in addition to the improvement of the neuroplasticity markers. Conclusions: The enhancing effect of BBR- NPs could be related to the enhancing of its bioavailability, absorption and brain drug uptake which need more investigation in future work.

Formononetin Ameliorates Cognitive Disorder via PGC-1α Pathway in Neuroinflammation Conditions in High-Fat Diet-Induced Mice

2019 ◽  
Vol 18 (7) ◽  
pp. 566-577 ◽  
Author(s):  
Xinxin Fu ◽  
Tingting Qin ◽  
Jiayu Yu ◽  
Jie Jiao ◽  
Zhanqiang Ma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Fat Diet ◽  
Trifolium Pratense ◽  
Amyloid Β ◽  
Cognitive Disorder ◽  
Mechanism Study ◽  
High Fat ◽  
Neuroprotective Effects ◽  
Underlying Mechanisms

Background: Alzheimer’s disease is one of the most common neurodegenerative diseases in many modern societies. The core pathogenesis of Alzheimer’s disease includes the aggregation of hyperphosphorylated Tau and abnormal Amyloid-β generation. In addition, previous studies have shown that neuroinflammation is one of the pathogenesis of Alzheimer’s disease. Formononetin, an isoflavone compound extracted from Trifolium pratense L., has been found to have various properties including anti-obesity, anti-inflammation, and neuroprotective effects. But there are very few studies on the treatment of Alzheimer’s disease with Formononetin. Objective: The present study focused on the protective activities of Formononetin on a high-fat dietinduced cognitive decline and explored the underlying mechanisms. Methods: Mice were fed with HFD for 10 weeks and intragastric administrated daily with metformin (300 mg/kg) and Formononetin (20 and 40 mg/kg). Results: We found that Formononetin (20, 40 mg/kg) significantly attenuated the learning and memory deficits companied by weight improvement and decreased the levels of blood glucose, total cholesterol and triglyceride in high-fat diet-induced mice. Meanwhile, we observed high-fat diet significantly caused the Tau hyperphosphorylation in the hippocampus of mice, whereas Formononetin reversed this effect. Additionally, Formononetin markedly reduced the levels of inflammation cytokines IL-1β and TNF-α in high-fat diet-induced mice. The mechanism study showed that Formononetin suppressed the pro-inflammatory NF-κB signaling and enhanced the anti-inflammatory Nrf-2/HO-1 signaling, which might be related to the regulation of PGC-1α in the hippocampus of high-fat diet -induced mice. Conclusion: Taken together, our results showed that Formononetin could improve the cognitive function by inhibiting neuroinflammation, which is attributed to the regulation of PGC-1α pathway in HFD-induced mice.

scholarly journals Temporal trajectory of biofluid markers in Parkinson’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Min Seok Baek ◽  
Myung Jun Lee ◽  
Han-Kyeol Kim ◽  
Chul Hyoung Lyoo
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Amyloid Β ◽  
Rapid Progression ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Using Data ◽  
Negative Exponential ◽  
T Tau

AbstractFull dynamics of biofluid biomarkers have been unknown in patients with Parkinson’s disease (PD). Using data from 396 PD patients and 182 controls in the Parkinson's Progression Markers Initiative (PPMI) database, we estimated long-term temporal trajectories of CSF α-synuclein (α-syn), amyloid-β (Aβ), total tau (t-tau), phosphorylated tau (p-tau) and serum neurofilament light chain (NfL) by integrating function between the baseline levels and annual changes. At baseline, PD patients showed lower CSF α-syn, Aβ, t-tau and p-tau levels than those of the controls. In all PD patients, CSF α-syn and Aβ decreased in a negative exponential pattern before the onset of motor symptoms, whereas CSF t-tau and p-tau, and serum NfL increased. Patients with cognitive impairment exhibited faster decline of Aβ and α-syn and faster rise of t-tau, p-tau and NfL, when compared to those without. Similarly, low Aβ group showed earlier decline of α-syn, faster rise of t-tau, p-tau and NfL, and faster decline of cognitive performances, when compared to high Aβ group. Our results suggest that longitudinal changes in biomarkers can be influenced by cognitive impairment and Aβ burden at baseline. PD patients with Aβ pathology may be associated with early appearance of α-synuclein pathology, rapid progression of axonal degeneration and neurodegeneration, and consequently greater cognitive decline.

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.

scholarly journals Interleukin-1β mediates alterations in mitochondrial fusion/fission proteins and memory impairment induced by amyloid-β oligomers

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Andre F. Batista ◽  
Tayná Rody ◽  
Leticia Forny-Germano ◽  
Suzana Cerdeiro ◽  
Maria Bellio ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mitochondrial Dysfunction ◽  
Memory Impairment ◽  
Mitochondrial Dynamics ◽  
Interleukin 1 ◽  
Amyloid Β ◽  
Mitochondrial Fusion ◽  
Synapse Loss ◽  
Cynomolgus Macaques ◽  
The Impact

Abstract Background The lack of effective treatments for Alzheimer’s disease (AD) reflects an incomplete understanding of disease mechanisms. Alterations in proteins involved in mitochondrial dynamics, an essential process for mitochondrial integrity and function, have been reported in AD brains. Impaired mitochondrial dynamics causes mitochondrial dysfunction and has been associated with cognitive impairment in AD. Here, we investigated a possible link between pro-inflammatory interleukin-1 (IL-1), mitochondrial dysfunction, and cognitive impairment in AD models. Methods We exposed primary hippocampal cell cultures to amyloid-β oligomers (AβOs) and carried out AβO infusions into the lateral cerebral ventricle of cynomolgus macaques to assess the impact of AβOs on proteins that regulate mitochondrial dynamics. Where indicated, primary cultures were pre-treated with mitochondrial division inhibitor 1 (mdivi-1), or with anakinra, a recombinant interleukin-1 receptor (IL-1R) antagonist used in the treatment of rheumatoid arthritis. Cognitive impairment was investigated in C57BL/6 mice that received an intracerebroventricular (i.c.v.) infusion of AβOs in the presence or absence of mdivi-1. To assess the role of interleukin-1 beta (IL-1β) in AβO-induced alterations in mitochondrial proteins and memory impairment, interleukin receptor-1 knockout (Il1r1−/−) mice received an i.c.v. infusion of AβOs. Results We report that anakinra prevented AβO-induced alteration in mitochondrial dynamics proteins in primary hippocampal cultures. Altered levels of proteins involved in mitochondrial fusion and fission were observed in the brains of cynomolgus macaques that received i.c.v. infusions of AβOs. The mitochondrial fission inhibitor, mdivi-1, alleviated synapse loss and cognitive impairment induced by AβOs in mice. In addition, AβOs failed to cause alterations in expression of mitochondrial dynamics proteins or memory impairment in Il1r1−/− mice. Conclusion These findings indicate that IL-1β mediates the impact of AβOs on proteins involved in mitochondrial dynamics and that strategies aimed to prevent pathological alterations in those proteins may counteract synapse loss and cognitive impairment in AD.

Effects of Folic Acid Combined with DHA Supplementation on Cognitive Function and Amyloid-β-Related Biomarkers in Older Adults with Mild Cognitive Impairment by a Randomized, Double Blind, Placebo-Controlled Trial

2021 ◽  
pp. 1-13
Author(s):  
Dong Bai ◽  
Junting Fan ◽  
Mengyue Li ◽  
Cuixia Dong ◽  
Yiming Gao ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Folic Acid ◽  
Mild Cognitive Impairment ◽  
Cognitive Function ◽  
Digit Span ◽  
Controlled Trial ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Double Blind ◽  
Full Scale Intelligence Quotient

Background: The neuroprotective benefits of combined folic acid and docosahexaenoic acid (DHA) on cognitive function in mild cognitive impairment (MCI) patients are suggested but unconfirmed. Objective: To explore the effects of 6-month folic acid + DHA on cognitive function in patients with MCI. Methods: Our randomized controlled trial (trial number ChiCTR-IOR-16008351) was conducted in Tianjin, China. We divided 160 MCI patients aged >  60 years into four regimen groups randomly: folic acid (0.8 mg/day) + DHA (800 mg/day), folic acid (0.8 mg/day), DHA (800 mg/day), and placebo, for 6 months. Cognitive function and blood amyloid-β peptide (Aβ) biomarker levels were measured at baseline and 6 months. Cognitive function was also measured at 12 months. Results: A total of 138 patients completed this trial. Folic acid improved the full-scale intelligence quotient (FSIQ), arithmetic, and picture complement scores; DHA improved the FSIQ, information, arithmetic, and digit span scores; folic acid + DHA improved the arithmetic (difference 1.67, 95% CI 1.02 to 2.31) and digital span (1.33, 0.24 to 2.43) scores compared to placebo. At 12 months, all scores declined in the intervention groups. Folic acid and folic acid + DHA increased blood folate (folic acid + DHA: 7.70, 3.81 to 11.59) and S-adenosylmethionine (23.93, 1.86 to 46.00) levels and reduced homocysteine levels (–6.51, –10.57 to –2.45) compared to placebo. DHA lower the Aβ40 levels (–40.57, –79.79 to –1.35) compared to placebo (p <  0.05), and folic acid + DHA reduced the Aβ42 (–95.59, –150.76 to –40.43) and Aβ40 levels (–45.75, –84.67 to –6.84) more than DHA (p <  0.05). Conclusion: Folic acid and DHA improve cognitive function and reduce blood Aβ production in MCI patients. Combination therapy may be more beneficial in reducing blood Aβ-related biomarkers.

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