Neuroprotective Effects of Ferruginol, Jatrophone, and Junicedric Acid Against Amyloid-β Injury in Hippocampal Neurons

2018 ◽  
Vol 63 (2) ◽  
pp. 705-723 ◽  
Author(s):  
Juan M. Zolezzi ◽  
Carolina B. Lindsay ◽  
Felipe G. Serrano ◽  
Roxana C. Ureta ◽  
Cristina Theoduloz ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Amyloid Β ◽  
Neuroprotective Effects

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.

scholarly journals Protein Kinase C Involvement in Neuroprotective Effects of Thymol and Carvacrol Against Toxicity Induced by Amyloid-Β in Rat Hippocampal Neurons

2021 ◽  
Author(s):  
Zahra Azizi ◽  
◽  
Samira Choopani ◽  
Mona Salimi ◽  
Nahid Majlessi ◽  
...  
Keyword(s):  
Rat Model ◽  
Cognitive Abilities ◽  
Hippocampal Neurons ◽  
Amyloid Β ◽  
Underlying Mechanism ◽  
Control Group ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Expression Ratio

Introduction: We have reported that thymol and carvacrol can improve cognitive abilities in Alzheimer’s disease (AD) rat model. However, the mechanism of their action is not yet fully understood. Recently, our in vitro results suggested that PC12 cell death-induced by Aβ25-35 can be protected by thymol and carvacrol via PKC and ROS pathways. So, we hypothesize that the mechanisms of thymol and carvacrol in improving the learning impairment in AD rat model may be related to their effects on PKC. So, the activity of PKC and protein expression levels of PKCα was examined in the hippocampal cells of AD rat model. Methods: To examine thymol and carvacrol effects, we performed behavioral test in AD rat model induced by Aβ25–35 neurotoxicity. To access the underlying mechanism of protective effects, western blotting was performed with antibodies against PKCα. We also measured PKC activity assay by Elisa. Histopathological studies were carried out in hippocampus by hematoxylin & eosin (H&E). Results: It was shown that escape latency increased in Aβ-received rats compared to control group and thymol and carvacrol reversed this deficit. Furthermore, these compouds could enhance PKC activity, and increase the PKCα expression ratio. Moreover, H&E showed that Aβ caused shrinkage of the CA1 pyramidal neurons. However, thymol and carvacrol treatments could prevent this effect of Aβ peptides. Conclusions: This study suggests that Aβ results in memory decline and histochemical disturbances in hippocampus. Moreover, these results revealed that thymol and carvacrol could have protective effects on cognition in AD-like models via PKC activation.

Astrocytic Expression of the Immunoreceptor CD300f Protects Hippocampal Neurons from Amyloid-β Oligomer Toxicity In Vitro

2017 ◽  
Vol 14 (7) ◽  
Author(s):  
Thiago Zaqueu Lima ◽  
Luis Roberto Sardinha ◽  
Joan Sayos ◽  
Luiz Eugenio Mello ◽  
Hugo Peluffo
Keyword(s):  
Hippocampal Neurons ◽  
Amyloid Β ◽  
Toxicity In Vitro

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.

Schisandrin Restores the Amyloid β-Induced Impairments on Mitochondrial Function, Energy Metabolism, Biogenesis, and Dynamics in Rat Primary Hippocampal Neurons

Pharmacology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Zhongyuan Piao ◽  
Lin Song ◽  
Lifen Yao ◽  
Limei Zhang ◽  
Yichan Lu
Keyword(s):  
Energy Metabolism ◽  
Cytochrome C ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Hippocampal Neurons ◽  
Citrate Synthase ◽  
Mitochondrial Permeability Transition ◽  
Amyloid Β ◽  
Mitochondrial Functions ◽  
Primary Hippocampal Neurons

Introduction: Schisandrin which is derived from Schisandra chinensis has shown multiple pharmacological effects on various diseases including Alzheimer’s disease (AD). It is demonstrated that mitochondrial dysfunction plays an essential role in the pathogenesis of neurodegenerative disorders. Objective: Our study aims to investigate the effects of schisandrin on mitochondrial functions and metabolisms in primary hippocampal neurons. Methods: In our study, rat primary hippocampal neurons were isolated and treated with indicated dose of amyloid β1–42 (Aβ1–42) oligomer to establish a cell model of AD in vitro. Schisandrin (2 μg/mL) was further subjected to test its effects on mitochondrial function, energy metabolism, mitochondrial biogenesis, and dynamics in the Aβ1–42 oligomer-treated neurons. Results and Conclusions: Our findings indicated that schisandrin significantly alleviated the Aβ1–42 oligomer-induced loss of mitochondrial membrane potential and impaired cytochrome c oxidase activity. Additionally, the opening of mitochondrial permeability transition pore and release of cytochrome c were highly restricted with schisandrin treatment. Alterations in cell viability, ATP production, citrate synthase activity, and the expressions of glycolysis-related enzymes demonstrated the relief of defective energy metabolism in Aβ-treated neurons after the treatment of schisandrin. For mitochondrial biogenesis, elevated expression of peroxisome proliferator-activated receptor γ coactivator along with promoted mitochondrial mass was found in schisandrin-treated cells. The imbalance in the cycle of fusion and fission was also remarkably restored by schisandrin. In summary, this study provides novel mechanisms for the protective effect of schisandrin on mitochondria-related functions.

scholarly journals A Super-Resolved View of the Alzheimer’s Disease-Related Amyloidogenic Pathway in Hippocampal Neurons

2021 ◽  
pp. 1-20
Author(s):  
Yang Yu ◽  
Yang Gao ◽  
Bengt Winblad ◽  
Lars Tjernberg ◽  
Sophia Schedin Weiss
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hippocampal Neurons ◽  
Three Dimensional ◽  
Amyloid Β ◽  
Stimulated Emission ◽  
Amyloid Β Peptide ◽  
Primary Neurons ◽  
Amyloid Β Protein ◽  
Early Endosomes

Background: Processing of the amyloid-β protein precursor (AβPP) is neurophysiologically important due to the resulting fragments that regulate synapse biology, as well as potentially harmful due to generation of the 42 amino acid long amyloid β-peptide (Aβ 42), which is a key player in Alzheimer’s disease. Objective: Our aim was to clarify the subcellular locations of the amyloidogenic AβPP processing in primary neurons, including the intracellular pools of the immediate substrate, AβPP C-terminal fragment (APP-CTF) and the product (Aβ 42). To overcome the difficulties of resolving these compartments due to their small size, we used super-resolution microscopy. Methods: Mouse primary hippocampal neurons were immunolabelled and imaged by stimulated emission depletion (STED) microscopy, including three-dimensional, three-channel imaging and image analyses. Results: The first (β-secretase) and second (γ-secretase) cleavages of AβPP were localized to functionally and distally distinct compartments. The β-secretase cleavage was observed in early endosomes, where we were able to show that the liberated N- and C-terminal fragments were sorted into distinct vesicles budding from the early endosomes in soma. Lack of colocalization of Aβ 42 and APP-CTF in soma suggested that γ-secretase cleavage occurs in neurites. Indeed, APP-CTF was, in line with Aβ 42 in our previous study, enriched in the presynapse but absent from the postsynapse. In contrast, full-length AβPP was not detected in either the pre- or the postsynaptic side of the synapse. Furthermore, we observed that endogenously produced and endocytosed Aβ 42 were localized in different compartments. Conclusion: These findings provide critical super-resolved insight into amyloidogenic AβPP processing in primary neurons.

Neuroprotective Effects of the FGF21 Analogue LY2405319

2021 ◽  
pp. 1-13
Author(s):  
Claire Rühlmann ◽  
David Dannehl ◽  
Marcus Brodtrück ◽  
Andrew C. Adams ◽  
Jan Stenzel ◽  
...  
Keyword(s):  
Glial Cells ◽  
Neuroprotective Effect ◽  
Amyloid Β ◽  
Fibroblast Growth Factor 21 ◽  
Neuroprotective Effects ◽  
Organotypic Brain Slice ◽  
Brain Slice Cultures ◽  
Abca1 Mrna

Background: To date, there are no effective treatments for Alzheimer’s disease (AD). Thus, a significant need for research of therapies remains. Objective: One promising pharmacological target is the hormone fibroblast growth factor 21 (FGF21), which is thought to be neuroprotective. A clinical candidate for medical use could be the FGF21 analogue LY2405319 (LY), which has a specificity and potency comparable to FGF21. Methods: The present study investigated the potential neuroprotective effect of LY via PPARγ/apoE/abca1 pathway which is known to degrade amyloid-β (Aβ) plaques by using primary glial cells and hippocampal organotypic brain slice cultures (OBSCs) from 30- and 50-week-old transgenic APPswe/PS1dE9 (tg) mice. By LY treatment of 52-week-old tg mice with advanced Aβ deposition, we further aimed to elaborate the effect of LY on AD pathology in vivo. Results: LY application to primary glial cells caused an upregulation of pparγ, apoE, and abca1 mRNA expression and significantly decreased number and area of Aβ plaques in OBSCs. LY treatment in tg mice increased cerebral [18F] FDG uptake and N-acetylaspartate/creatine ratio indicating enhanced neuronal activity and integrity. Although LY did not reduce the number of Aβ plaques in tg mice, the number of iba1-positive cells was significantly decreased indicating reduced microgliosis. Conclusion: These data identified LY in vitro as an activator of Aβ degrading genes leading to cerebral Aβ load amelioration in early and late AD pathology. Although Aβ plaque reduction by LY failed in vivo, LY may be used as therapeutic agent to treat AD-related neuroinflammation and impaired neuronal integrity.

Amyloid β-peptide(25-35) changes [Ca2+] in hippocampal neurons

Neuroreport ◽  
1998 ◽  
Vol 9 (7) ◽  
pp. 1553-1558 ◽  
Author(s):  
Helle S. Mogensen ◽  
Diane M. Beatty ◽  
Stephen J. Morris ◽  
Ole Steen Jorgensen
Keyword(s):  
Hippocampal Neurons ◽  
Amyloid Β ◽  
Amyloid Β Peptide
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