Atorvastatin Relieves Cognitive Disorder After Sepsis Through Reverting Inflammatory Cytokines, Oxidative Stress, and Neuronal Apoptosis in Hippocampus

Tian, Jianmei; Tai, Yongjie; Shi, Mengrao; Zhao, Chunxiu; Xu, Wenwen; Ge, Xuhua; Zhu, Guoji

doi:10.1007/s10571-019-00750-z

Cited by 18 publications

(10 citation statements)

References 32 publications

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“…Similar to our ndings, endotoxin LPS, an in ammatory stimulator, has been reported to induce cognitive de cits in mice through neuroin ammation and neuronal apoptosis [16]. Inhibition of in ammatory cytokines, oxidative stress, and neuronal apoptosis in the hippocampus also ameliorated cognitive de cits in mouse model of AD [50], vascular dementia and Sepsis [51].…”

Section: Discussionsupporting

confidence: 88%

Microglial Activation Contributes to Cognitive Impairments in Rotenone-induced Mouse Parkinson’s Disease Model

Zhang

Hou

et al. 2020

Preprint

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BackgroundCognitive decline occurs frequently in Parkinson’s disease (PD), which greatly decreases the life quality of patients. However, the mechanisms remain to be investigated. Neuroinflammation mediated by over-activated microglia is a common pathological feature in multiple neurological disorders, including PD. This study is designed to explore the role of microglia in cognitive deficits by using rotenone-induced mouse PD model. Methods: To evaluate the role of microglia in rotenone-induced cognitive deficits, PLX3397, an inhibitor of colony-stimulating factor 1 receptor, and minocycline, a widely used antibiotic, were used to deplete or inactivate microglia, respectively. Cognitive performance of mice among groups was detected by morris water maze, objective recognition and passive avoidance tests. Neurodegeneration, synaptic loss, α-synuclein phosphorylation, glial activation and apoptosis were determined by immunohistochemistry, Western blot or immunofluorescence staining. The gene expressions of inflammatory factors and lipid peroxidation were further explored by using RT-PCR and ELISA kits, respectively. ResultsRotenone dose-dependently induced cognitive deficits in mice by showing decreased abilities of novel objective recognition, passive avoidance, as well as morris water maze performance compared with vehicle controls. Rotenone-induced cognitive decline was associated with neurodegeneration, synaptic loss, Ser129-phosphorylation of α-synuclein and microglial activation in the hippocampal and cortical regions of mice. Time course study revealed that rotenone-induced microglial activation preceded neurodegeneration. Interestingly, microglial depletion by PLX3397 or inactivation by minocycline significantly reduced neuronal damage and α-synuclein pathology as well as improved cognitive performance in rotenone-injected mice. Mechanistically, PLX3397 or minocycline attenuated rotenone-induced astroglial activation and production of cytotoxic factors in mice. Reduced lipid peroxidation was also observed in combined PLX3397 or minocycline and rotenone-treated mice compared with rotenone alone group. Finally, microglial depletion or inactivation was found to mitigate rotenone-induced neuronal apoptosis. ConclusionsTaken together, our findings suggested that microglial activation contributed to cognitive impairments in rotenone-induced mouse PD model via neuroinflammation, oxidative stress and apoptosis, providing novel insight for the immunopathogensis of cognitive deficits in PD.

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Section: Discussionsupporting

confidence: 88%

Microglial Activation Contributes to Cognitive Impairments in Rotenone-induced Mouse Parkinson’s Disease Model

Zhang

Hou

et al. 2020

Preprint

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“…Although we assessed inflammatory mediators, we did not detect oxidative stress biomarkers, which were also reported to be involved in SAE-induced learning and memory impairment. 88 , 89 2. In this study, we assessed the learning and memory ability, VP level, cytokine levels, and BDNF levels at a single time point (ie, after 30 days of housing).…”

Section: Discussionmentioning

confidence: 99%

Environmental Enrichment Protects Against Sepsis-Associated Encephalopathy-Induced Learning and Memory Deficits by Enhancing the Synthesis and Release of Vasopressin in the Supraoptic Nucleus

Jiang¹,

Wang²,

Tang³

et al. 2022

JIR

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Background As a severe complication of sepsis, sepsis-associated encephalopathy (SAE) usually manifests as impaired learning and memory ability in survivors. Previous studies have reported that environmental enrichment (EE) can increase the learning and memory ability in different brain injury models. However, there has been no research on the possible positive effect of EE on SAE. Aim The present study aimed to test the effect of EE on SAE-induced impairment of learning and memory and its related mechanisms. Methods A Morris water maze test (MWM) was used to evaluate the learning and memory ability of SAE rats that received EE housing or not. The expression of vasopressin (VP) was assessed using immunofluorescence microscopy and enzyme-linked immunosorbent assays (ELISAs). The synthesis of VP in the supraoptic nucleus (SON) was determined using quantitative real-time reverse transcription-PCR analysis. Moreover, inflammatory markers and brain-derived neurotrophic factor (BDNF) were detected using ELISA. Results The results showed that SAE induced a decreased learning and memory ability, while EE reversed this impairment. EE also enhanced the synthesis and secretion of VP in the SON. Blocking the action of VP in the hippocampus interrupted the EE-induced amelioration of learning and memory impairment. Moreover, EE induced changes to the levels of BDNF and cytokines in the hippocampus and these effects were mediated by VP binding to the VP receptor 1a. Conclusion Our findings demonstrated that the enhanced synthesis and secretion of VP in the SON are a key determinant responsible for EE-induced alleviation of learning and memory deficits caused by SAE.

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“…Robust evidence indicates that atorvastatin may be helpful in treating various cardiovascular diseases, such as coronary heart disease, atherosclerosis, and hypertension. Tian and coworkers [ 3 ] found that atorvastatin improved cognitive disorders in a sepsis mouse model by mediating inflammatory cytokines, oxidative stress, and neuronal apoptosis in the hippocampus. Thassakorn et al [ 16 ] reported that atorvastatin exerts antioxidant and anti-inflammatory effects in dogs with heart failure.…”

Section: Discussionmentioning

confidence: 99%

“…Statins, which inhibit 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) activity, are widely used in the treatment of dyslipidemia and to decrease the severity of other cardiovascular events in patients with coronary heart disease. More recently, pleiotropic protective effects of statins, including antioxidant, pro-apoptosis, and anti-inflammatory effects in vascular tissue, have been described [ 1 – 3 ]. These findings indicate that statins may have additional therapeutic uses.…”

Section: Introductionmentioning

confidence: 99%

Atorvastatin attenuates intermittent hypoxia-induced myocardial oxidative stress in a mouse obstructive sleep apnea model

Zhang

Cheng

Yuan

et al. 2021

Aging

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Chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnea (OSA), is associated with various cardiovascular diseases. In the present study, we assessed the effect of the lipid reducing agent atorvastatin on CIH-induced myocardial oxidative stress and apoptosis in a mouse OSA model. Forty-eight C57BL/6J mice were evenly divided among normoxia + vehicle, normoxia + atorvastatin, CIH + vehicle, and CIH + atorvastatin groups. CIH consisted of a hypoxia-reoxygenation cycle in which oxygen concentrations fluctuated from 21% to 6% and back over two minutes for 8 hours each day (30 events/hour). CIH exposure continued for 12 weeks. Atorvastatin (5 mg/kg) was administered from week 6 through the end of the experiment. CIH increased malondialdehyde levels and decreased superoxide dismutase activity, total antioxidant capacity, and nuclear factor erythroid 2-related factor 2 levels in cardiac tissue, indicating a reduction in antioxidant activity. Atorvastatin significantly reversed those effects ( p < 0.05). CIH also increased B-cell lymphoma 2-associated protein X and cleaved caspased-3 levels as well as the myocardial apoptotic rate, as indicated by terminal deoxynucleotidyl transferase dUTP nick-end labeling. Atorvastatin had no effect on those changes ( p > 0.05). Thus, atorvastatin administration exerts antioxidant but not anti-apoptotic effects after CIH and may therefore have therapeutic potential in OSA patients with cardiovascular comorbidities.

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Atorvastatin Relieves Cognitive Disorder After Sepsis Through Reverting Inflammatory Cytokines, Oxidative Stress, and Neuronal Apoptosis in Hippocampus

Cited by 18 publications

References 32 publications

Microglial Activation Contributes to Cognitive Impairments in Rotenone-induced Mouse Parkinson’s Disease Model

Microglial Activation Contributes to Cognitive Impairments in Rotenone-induced Mouse Parkinson’s Disease Model

Environmental Enrichment Protects Against Sepsis-Associated Encephalopathy-Induced Learning and Memory Deficits by Enhancing the Synthesis and Release of Vasopressin in the Supraoptic Nucleus

Atorvastatin attenuates intermittent hypoxia-induced myocardial oxidative stress in a mouse obstructive sleep apnea model

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