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.

Vitamin D Alleviates Cognitive Dysfunction by Activating the VDR/ERK1/2 Signaling Pathway in an Alzheimer’s Disease Mouse Model

2020 ◽  
Vol 27 (4) ◽  
pp. 178-185
Author(s):  
Zheng Bao ◽  
Xue Wang ◽  
Yuhong Li ◽  
Fumin Feng
Keyword(s):  
Vitamin D ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Signaling Pathway ◽  
Learning And Memory ◽  
Hippocampal Neurons ◽  
Morphological Changes ◽  
Active Form ◽  
Biologically Active ◽  
Neuroprotective Effects

Objective: Vitamin D (Vit D), a steroid hormone, has been linked to cognitive impairment and dementia, such as Alz­heimer’s disease (AD). 1, 25(OH)2D3 is the biologically active form of Vit D, which has been shown to have neuroprotective effects. This compound is being evaluated as an emerging therapeutic treatment in models of AD. Material and Methods: The present study was designed to investigate whether Vit D could alleviate cognitive impairment in an AD rat model by regulating the VDR/ERK1/2 signaling pathway. Adult male APPswe/PS1ΔE9 rats (n = 40) were randomly divided into 2 groups: the AD group and the Vit D + AD group (20 mice per group), and 40 C57BL/6J age-matched mice were separated into the control (CON) group and the Vit D + CON group (20 mice per group). The Morris water maze and object recognition tests were used to evaluate learning and memory functions of the mice. Hematoxylin and eosin staining was used to evaluate morphological changes in hippocampal neurons. Western blotting was used to evaluate the proteins responsible for these changes. Results: We found that Vit D improved learning and memory abilities and morphological defects in hippocampal neurons. Vit D decreased the gene expression of caspase-3 and Bax and increased the expression of Bcl-2. Vit D also increased the protein expression of VDR and p-ERK1 protein in AD mice. Conclusion: This study provides new clues about the mechanism by which Vit D exerts neuroprotective effects in an AD mouse model.

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.

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

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

scholarly journals Curcumin protects rat hippocampal neurons against pseudorabies virus by regulating the BDNF/TrkB pathway

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Bingjie Yang ◽  
Guodong Luo ◽  
Chen Zhang ◽  
Luqiu Feng ◽  
Xianmei Luo ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Hippocampal Neurons ◽  
Pseudorabies Virus ◽  
Underlying Mechanism ◽  
Protective Effects ◽  
Apoptotic Pathway ◽  
Neuroprotective Effects ◽  
Tropomyosin Related Kinase B ◽  
Underlying Mechanisms ◽  
Oxide Synthase

AbstractPseudorabies virus (PRV) infection can elicit nervous system disorders. Curcumin has been reported to have neuroprotective effects. However, whether curcumin can protect neurons against PRV infection and the underlying mechanisms remain unclear. In the present study, for the first time, the protective effects of curcumin against PRV-induced oxidative stress, apoptosis, and mitochondrial dysfunction in rat hippocampal neurons and the brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway were investigated. Results indicated that PRV with a titer of 3.06 × 106 TCID50 (50% tissue culture infective dose) induced oxidative damage of hippocampal neurons 2 h post-infection and that 10 μM curcumin improved the viability of PRV-infected hippocampal neurons. Blocking the BDNF/TrkB pathway reversed the neuroprotective effects of curcumin, which were imparted by decreasing the PRV-induced upregulation of nitric oxide synthase expression, repressing the PRV-activated mitochondrial apoptotic pathway, and mitochondrial dysfunction. To conclude, curcumin exhibited a neuroprotective role against PRV infection by upregulating the BDNF/TrkB pathway. This study provides insight into the anti-PRV neuroprotective application of curcumin and the underlying mechanism in the prophylaxis and treatment of neurological disorders caused by PRV infection.

scholarly journals Roscovitine, a CDK5 Inhibitor, Alleviates Sevoflurane-Induced Cognitive Dysfunction via Regulation Tau/GSK3β and ERK/PPARγ/CREB Signaling

2017 ◽  
Vol 44 (2) ◽  
pp. 423-435 ◽  
Author(s):  
Jianhui Liu ◽  
Junjun Yang ◽  
Yinhua Xu ◽  
Gang Guo ◽  
Li Cai ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Dysfunction ◽  
Hippocampal Neurons ◽  
Glycogen Synthase ◽  
Neuronal Damage ◽  
Immunohistochemical Analysis ◽  
Peroxisome Proliferator ◽  
Neuroprotective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ

Background/Aims: Multiple exposures to anesthesia in children may increase the risk of developing cognitive impairment. Sevoflurane is an anesthetic that is commonly used in children during surgery. Cyclin-dependent kinase (CDK) 5 is involved in the regulation of sevoflurane-induced cognitive dysfunction, but the mechanistic details remain unclear. The present study evaluated the mechanism by which CDK5 mediates sevoflurane-induced cognitive dysfunction in mice. Methods: Hippocampal neurons were isolated from postnatal day 0 C57BL/6 mouse pups. Six-day-old wild-type mice were exposed to sevoflurane and then treated with the CDK5 inhibitor roscovitine. The effects on cognitive function were evaluated with the Morris water maze and neuronal damage in the hippocampus was assessed by immunohistochemical analysis. Results: CDK5 activation increased neuronal damage by inducing Tau/glycogen synthase kinase (GSK) 3β and suppressing extracellular signal-regulated kinase (ERK)/peroxisome proliferator-activated receptor (PPAR)γ/cyclic AMP response element-binding protein (CREB) signaling following exposure to sevoflurane. CDK5 inhibition by roscovitine administration alleviated sevoflurane-induced neuronal damage and cognitive impairment. Conclusions: Inhibiting CDK5 with roscovitine has neuroprotective effects against neuronal injury and cognitive dysfunction caused by sevoflurane anesthesia that are exerted via modulation of Tau/GSK3β and ERK/PPARγ/CREB signaling.

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