scholarly journals Baicalein Ameliorates Aβ-Induced Memory Deficits and Neuronal Atrophy via Inhibition of PDE2 and PDE4

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Shi ◽  
Yuanyuan Li ◽  
Yi Zhang ◽  
Jie Chen ◽  
Jianqing Gao ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Amyloid Β ◽  
Cognitive Disorder ◽  
Synaptic Proteins ◽  
Intracellular Camp ◽  
The Novel ◽  
Scutellaria Baicalensis Georgi ◽  
Neuronal Remodeling ◽  
Wide Range ◽  
Memory Acquisition

Inhibition of phosphodiesterase 2 and 4 (PDE2A and PDE4) increases the intracellular cAMP and/or cGMP levels, which may prevent Amyloid β 42 oligomers (Aβ) related cognitive impairment and dementias. Baicalein, one of natural flavones found in the root of Scutellaria baicalensis Georgi, has a wide range of pharmacological activities including antioxidant and anti-inflammatory effects. However, no studies suggest whether baicalein mediated anti-Alzheimer’s disease (AD) events involve PDEs subtypes-mediated neuroprotective pathways. The present study examined whether memory enhancing effects of baicalein on Aβ- induced cognitive impairment are related to regulating neuroplasticity via PDE2 and PDE4 subtypes dependent cAMP/cGMP neuroprotective pathway. The results suggested that microinjected of Aβ into CA1 of hippocampus induced cognitive and memory impairment in mice, as evidenced by decreased recognition index in the novel object recognition (NOR) task, impaired memory acquisition, retention and retrieval in the Morris water maze (MWM) and shuttle box tests. These effects were reversed by treatment with baicalein for 14 days. Moreover, Aβ-induced neuronal atrophy and decreased expression of two synaptic proteins, synaptophysin and PSD 95, were prevented by baicalein. The increased expression of PDE2A and PDE4 subtypes (PDE4A, PDE4B and PDE4D), and decreased levels of cAMP/cGMP, pCREB/CREB and BDNF induced by Aβ were also blocked by chronic treatment of baicalein for 14 days. These findings suggest that baicalein’s reversal of Aβ-induced memory and cognitive disorder may involve the regulation of neuronal remodeling via regulation of PDE2/PDE4 subtypes related cAMP/cGMP -pCREB-BDNF pathway.

COGNITIVE IMPAIRMENT IN PATIENTS WITH CORONAVIRUS INFECTION

2021 ◽  
Vol 2 (1) ◽  
pp. 5-8
Author(s):  
Gulnoza Urinova ◽  
◽  
Nargiza Nasirtdinova ◽  
Janna Nazarova
Keyword(s):  
Cognitive Impairment ◽  
Neurological Disorders ◽  
Sinus Thrombosis ◽  
The Novel ◽  
Altered Level ◽  
Wide Range ◽  
Level Of Consciousness ◽  
Coronavirus Infection ◽  
Novel Coronavirus ◽  
The Brain

Thisarticle discusses cognitive impairment in patients with coronavirus infection and explains that observations have been made on this topic. The novel coronavirus infection COVID-19 caused by the SARS-CoV-2 coronavirus poses a global health threat. Neurological disordersfound in patients with coronavirus infection have a wide range of clinical neurological signs: headache, dizziness, altered level of consciousness, acute cerebrovascular accident (ACVE), venous sinus thrombosis the brain [12].Keywords:coronavirus infection, cognitive impairment, neurological disorders, headache, dizziness, muscle weakness, encephalopathy, encephalitis

Resveratrol Rescues Tau-Induced Cognitive Deficits and Neuropathology in a Mouse Model of Tauopathy

2019 ◽  
Vol 16 (8) ◽  
pp. 710-722 ◽  
Author(s):  
Xiao-Ying Sun ◽  
Quan-Xiu Dong ◽  
Jie Zhu ◽  
Xun Sun ◽  
Li-Fan Zhang ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Therapeutic Potential ◽  
Amyloid Β ◽  
Synaptic Proteins ◽  
Morris Water Maze Test ◽  
Phosphorylated Tau ◽  
Tau Pathology ◽  
Maze Test ◽  
N2a Cells ◽  
Tau Aggregation

Background: Alzheimer’s Disease (AD) is characterized by the presence of extracellular amyloid-β (Aβ) plaques and intraneuronal neurofibrillary tangles assembled by the microtubuleassociated protein tau. Increasing evidence demonstrated that tau pathology played an important role in AD progression. Resveratrol (RSV) has previously proved to exert neuroprotective effect against AD by inhibiting Aβ generation and Aβ-induced neurocytotoxicity, while its effect on tau pathology is still unknown. Method: The effect of RSV on tau aggregation was measured by Thioflavin T fluorescence and Transmission electron microscope imaging. The effect of RSV on tau oligomer-induced cytotoxicity was assessed by MTT assay and the uptake of extracellular tau by N2a cells was determined by immunocytochemistry. 6-month-old male PS19 mice were treated with RSV or vehicle by oral administration (gavage) once a day for 5 weeks. The cognitive performance was determined using Morris water maze test, object recognition test and Y-maze test. The levels of phosphorylated-tau, gliosis, proinflammatory cytokines such as TNF-α and IL-1β, and synaptic proteins including synaptophysin and PSD95 in the brains of the mice were evaluated by immunoblotting, immunostaining and ELISA, respectively. Results: RSV significantly inhibited tau aggregation and tau oligomer-induced cytotoxicity, and blocked the uptake of extracellular tau oligomers by N2a cells. When applied to PS19 mice, RSV treatment effectively rescued cognitive deficits, reducing the levels of phosphorylated tau, neuroinflammation and synapse loss in the brains of mice. Conclusion: These findings suggest that RSV has promising therapeutic potential for AD and other tauopathies.

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.

Reading Beyond the Code

2018 ◽  
Keyword(s):  
Relevance Theory ◽  
Literary Studies ◽  
The Novel ◽  
Human Communication ◽  
Communicative Acts ◽  
Face To Face ◽  
Code Model ◽  
Wide Range ◽  
Central Claim

This book explores the value for literary studies of relevance theory, an inferential approach to communication in which the expression and recognition of intentions plays a major role. Drawing on a wide range of examples from lyric poetry and the novel, nine of the ten chapters are written by literary specialists and use relevance theory both as an overall framework and as a resource for detailed analysis. The final chapter, written by the co-founder of relevance theory, reviews the issues addressed by the volume and explores their implications for cognitive theories of how communicative acts are interpreted in context. Originally designed to explain how people understand each other in everyday face-to-face exchanges, relevance theory—described in an early review by a literary scholar as ‘the makings of a radically new theory of communication, the first since Aristotle’s’—sheds light on the whole spectrum of human modes of communication, including literature in the broadest sense. Reading Beyond the Code is unique in using relevance theory as a prime resource for literary study, and is also the first to apply the model to a range of phenomena widely seen as supporting an ‘embodied’ conception of cognition and language where sensorimotor processes play a key role. This broadened perspective serves to enhance the value for literary studies of the central claim of relevance theory: that the ‘code model’ is fundamentally inadequate to account for human communication, and in particular for the modes of communication that are proper to literature.

scholarly journals The CoGenT3 Study: Cognition and Gender Trends in Three American Generations

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 817-817
Author(s):  
Shana Stites
Keyword(s):  
Cognitive Impairment ◽  
Quantitative Methods ◽  
Cognitive Testing ◽  
Library Science ◽  
Sexual And Gender Minorities ◽  
Functional Impairments ◽  
Gender Minorities ◽  
Wide Range ◽  
And Gender ◽  
New Research

Abstract Many studies find gender differences in how older adults’ report on their memory, perform on cognitive testing, and manage functional impairments that can accompany cognitive impairment. Thus, understanding gender’s effects in aging and Alzheimer’s research is key for advancing methods to prevent, slow, manage, and diagnosis cognitive impairment. Our study, CoGenT3 – The study of Cognition and Gender in Three Generations – seeks to disambiguate the effects of gender on cognition in order to inform a conceptual model, guide innovations in measurement, and support future study. To accomplish this ambitious goal, we have gathered an interdisciplinary team with expertise in psychology, cognition, sexual and gender minorities, library science, measurement, quantitative methods, qualitative methods, and gender and women’s studies. The team benefits from the intersections of expertise in being able to build new research ideas, gain novel insights, and evaluate a wide-range of actions and re-actions but this novelty can also raise challenges.

scholarly journals NLRP3 Inflammasome: A Starring Role in Amyloid-β- and Tau-Driven Pathological Events in Alzheimer’s Disease

2021 ◽  
pp. 1-22
Author(s):  
Mariana Van Zeller ◽  
Diogo M. Dias ◽  
Ana M. Sebastião ◽  
Cláudia A. Valente
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glial Cells ◽  
Neurofibrillary Tangles ◽  
Nlrp3 Inflammasome ◽  
Neuronal Death ◽  
Inflammatory Responses ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Wide Range

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease commonly diagnosed among the elderly population. AD is characterized by the loss of synaptic connections, neuronal death, and progressive cognitive impairment, attributed to the extracellular accumulation of senile plaques, composed by insoluble aggregates of amyloid-β (Aβ) peptides, and to the intraneuronal formation of neurofibrillary tangles shaped by hyperphosphorylated filaments of the microtubule-associated protein tau. However, evidence showed that chronic inflammatory responses, with long-lasting exacerbated release of proinflammatory cytokines by reactive glial cells, contribute to the pathophysiology of the disease. NLRP3 inflammasome (NLRP3), a cytosolic multiprotein complex sensor of a wide range of stimuli, was implicated in multiple neurological diseases, including AD. Herein, we review the most recent findings regarding the involvement of NLRP3 in the pathogenesis of AD. We address the mechanisms of NLRP3 priming and activation in glial cells by Aβ species and the potential role of neurofibrillary tangles and extracellular vesicles in disease progression. Neuronal death by NLRP3-mediated pyroptosis, driven by the interneuronal tau propagation, is also discussed. We present considerable evidence to claim that NLRP3 inhibition, is undoubtfully a potential therapeutic strategy for AD.

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 Pharmacological rescue of cognitive function in a mouse model of chemobrain

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Lien D. Nguyen ◽  
Tom T. Fischer ◽  
Barbara E. Ehrlich
Keyword(s):  
Cognitive Impairment ◽  
Prefrontal Cortex ◽  
Calcium Oscillations ◽  
Neuronal Morphology ◽  
Post Injection ◽  
Object Recognition Test ◽  
Cognitive Changes ◽  
Memory Acquisition ◽  
Underlying Mechanisms ◽  
Trisphosphate Receptor

Abstract Background After chemotherapy, many cancer survivors suffer from long-lasting cognitive impairment, colloquially known as “chemobrain.” However, the trajectories of cognitive changes and the underlying mechanisms remain unclear. We previously established paclitaxel-induced inositol trisphosphate receptor (InsP3R)-dependent calcium oscillations as a mechanism for peripheral neuropathy, which was prevented by lithium pretreatment. Here, we investigated if a similar mechanism also underlay paclitaxel-induced chemobrain. Method Mice were injected with 4 doses of 20 mg/kg paclitaxel every other day to induced cognitive impairment. Memory acquisition was assessed with the displaced object recognition test. The morphology of neurons in the prefrontal cortex and the hippocampus was analyzed using Golgi-Cox staining, followed by Sholl analyses. Changes in protein expression were measured by Western blot. Results Mice receiving paclitaxel showed impaired short-term spatial memory acquisition both acutely 5 days post injection and chronically 23 days post injection. Dendritic length and complexity were reduced in the hippocampus and the prefrontal cortex after paclitaxel injection. Concurrently, the expression of protein kinase C α (PKCα), an effector in the InsP3R pathway, was increased. Treatment with lithium before or shortly after paclitaxel injection rescued the behavioral, cellular, and molecular deficits observed. Similarly, memory and morphological deficits could be rescued by pretreatment with chelerythrine, a PKC inhibitor. Conclusion We establish the InsP3R calcium pathway and impaired neuronal morphology as mechanisms for paclitaxel-induced cognitive impairment. Our findings suggest lithium and PKC inhibitors as candidate agents for preventing chemotherapy-induced cognitive impairment.

scholarly journals VAMP-2 is a surrogate cerebrospinal fluid marker of Alzheimer-related cognitive impairment in adults with Down syndrome

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Alberto Lleó ◽  
Maria Carmona-Iragui ◽  
Laura Videla ◽  
Susana Fernández ◽  
Bessy Benejam ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Down Syndrome ◽  
Cognitive Impairment ◽  
Episodic Memory ◽  
Cognitive Performance ◽  
Synaptic Proteins ◽  
Selected Reaction Monitoring ◽  
Synaptic Protein ◽  
Csf Levels ◽  
Syntaxin 1B

Abstract Background There is an urgent need for objective markers of Alzheimer’s disease (AD)-related cognitive impairment in people with Down syndrome (DS) to improve diagnosis, monitor disease progression, and assess response to disease-modifying therapies. Previously, GluA4 and neuronal pentraxin 2 (NPTX2) showed limited potential as cerebrospinal fluid (CSF) markers of cognitive impairment in adults with DS. Here, we compare the CSF profile of a panel of synaptic proteins (Calsyntenin-1, Neuroligin-2, Neurexin-2A, Neurexin-3A, Syntaxin-1B, Thy-1, VAMP-2) to that of NPTX2 and GluA4 in a large cohort of subjects with DS across the preclinical and clinical AD continuum and explore their correlation with cognitive impairment. Methods We quantified the synaptic panel proteins by selected reaction monitoring in CSF from 20 non-trisomic cognitively normal controls (mean age 44) and 80 adults with DS grouped according to clinical AD diagnosis (asymptomatic, prodromal AD or AD dementia). We used regression analyses to determine CSF changes across the AD continuum and explored correlations with age, global cognitive performance (CAMCOG), episodic memory (modified cued-recall test; mCRT) and CSF biomarkers, CSF Aβ42:40 ratio, CSF Aβ1-42, CSF p-tau, and CSF NFL. P values were adjusted for multiple testing. Results In adults with DS, VAMP-2 was the only synaptic protein to correlate with episodic memory (delayed recall adj.p = .04) and age (adj.p = .0008) and was the best correlate of CSF Aβ42:40 (adj.p = .0001), p-tau (adj.p < .0001), and NFL (adj.p < .0001). Compared to controls, mean VAMP-2 levels were lower in asymptomatic adults with DS only (adj.p = .02). CSF levels of Neurexin-3A, Thy-1, Neurexin-2A, Calysntenin-1, Neuroligin-2, GluA4, and Syntaxin-1B all strongly correlated with NPTX2 (p < .0001), which was the only synaptic protein to show reduced CSF levels in DS at all AD stages compared to controls (adj.p < .002). Conclusion These data show proof-of-concept for CSF VAMP-2 as a potential marker of synapse degeneration that correlates with CSF AD and axonal degeneration markers and cognitive performance.

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