Maresin 1 attenuates neuroinflammation in a mouse model of perioperative neurocognitive disorders
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PROVIDER: PRJNA475007 | ENA |
REPOSITORIES: ENA
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Project description:Hippocampus-based mitochondrial respiratory function decline is responsible for perioperative neurocognitive disorders
| PRJNA741808 | ENA
Project description:Background: Perioperative neurocognitive disorders (PND), a postoperative cognitive dysfunction occurs more often in the elderly. The etiology of PND remains largely elusive. This study aims to understand the etiology in a mouse model with tibial fracture (a surgical trauma), by examining the transcriptome-wide response of hippocampus, a brain region that is tightly associated with memory formation. Methods: Mice at age of 7~8 months were randomly divided into two groups, surgery (tibial fracture) group and control (sham) group. At day (d) 1 after the surgical operation, hippocampal tissues were isolated and then subjected to RNA extraction and RNA sequencing (RNA-seq). Findings: Levels of respiratory complex related genes are significantly decreased in the brain of mice subjected to surgery. Consequently, the activities of multiple respiratory complexes and respiratory chain function is decreased in the hippocampus of mice with surgical operation. Interpretation: We here propose a novel mechanism of mitochondrial dysfunction in PND etiology, and also provide a potential therapeutic target for PND.
2022-02-09 | GSE178995 | GEO
Project description:Maresin 1 administered to mice prior to orthopedic surgery exerts distinct anti-inflammatory and pro-resolving effects through regulation of MΦ infiltration, NF-κB signaling, and cytokine release. We used microarrays to detail the global programme of gene expression underlying Maresin 1 effect on mouse hippocampus and identified distinct classes of dysregulated genes during this process.
2018-11-13 | GSE115440 | GEO
Project description:BACKGROUND:Resolution of inflammation is an active and dynamic process after surgery. Maresin 1 (MaR1) is one of a growing number of specialised pro-resolving lipids biosynthesised by macrophages that regulates acute inflammation. We investigated the effects of MaR1 on postoperative neuroinflammation, macrophage activity, and cognitive function in mice. METHODS:Adult male C57BL/6 (n=111) and Ccr2RFP/+Cx3cr1GFP/+ (n=54) mice were treated with MaR1 before undergoing anaesthesia and orthopaedic surgery. Systemic inflammatory changes, bone healing, neuroinflammation, and cognition were assessed at different time points. MaR1 protective effects were also evaluated using bone marrow derived macrophage cultures. RESULTS:MaR1 exerted potent systemic anti-inflammatory effects without impairing fracture healing. Prophylaxis with MaR1 prevented surgery-induced glial activation and opening of the blood-brain barrier. In Ccr2RFP/+Cx3cr1GFP/+ mice, fewer infiltrating macrophages were detected in the hippocampus after surgery with MaR1 prophylaxis, which resulted in improved memory function. MaR1 treatment also reduced expression of pro-inflammatory cell surface markers and cytokines by in vitro cultured macrophages. MaR1 was detectable in the cerebrospinal fluid of older adults before and after surgery. CONCLUSIONS:MaR1 exerts distinct anti-inflammatory and pro-resolving effects through regulation of macrophage infiltration, NF-?B signalling, and cytokine release after surgery. Future studies on the use of pro-resolving lipid mediators may inform novel approaches to treat neuroinflammation and postoperative neurocognitive disorders.
| S-EPMC6396737 | biostudies-literature
Project description:Perioperative neurocognitive dysfunction (PND) is emerging as a significant complication of surgery in elderly patients. However, the molecular mechanisms of PND are not well known. Here we applied microarray analysis to identify circular RNAs (circRNAs) in hippocampus from a mouse model of PND and control mice. Then, the dysregulated circRNAs were confirmed via quantitative real-time polymerase chain reaction (qRT-PCR). Then, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to probe the vital functions of dysregulated genes.
2021-08-10 | GSE165798 | GEO
Project description:Perioperative neurocognitive disorders are common in elderly patients who have undergone surgical procedures. Neuroinflammation induced by microglial activation is a hallmark of these neurological disorders. Acetate can suppress inflammation in the context of inflammatory diseases. We employed an exploratory laparotomy model with isoflurane anesthesia to study the effects of acetate on perioperative neurocognitive disorders in aged mice. Neurocognitive function was assessed with open-field tests and Morris water maze tests 3 or 7 days post-surgery. Acetate ameliorated the surgery-induced cognitive deficits of aged mice and inhibited the activation of IBA-1, a marker of microglial activity. Acetate also reduced expression of inflammatory proteins (tumor necrosis factor-α, interleukin-1β and interleukin-6), oxidative stress factors (NADPH oxidase 2, inducible nitric oxide synthase and reactive oxygen species), and signaling molecules (nuclear factor kappa B and mitogen-activated protein kinase) in the hippocampus. BV2 microglial cells were used to verify the anti-inflammatory effects of acetate in vitro. Acetate suppressed inflammation in lipopolysaccharide-treated BV2 microglial cells, but not when GPR43 was silenced. These results suggest that acetate may bind to GPR43, thereby inhibiting microglial activity, suppressing neuroinflammation, and preventing memory deficits. This makes acetate is a promising therapeutic for surgery-induced neurocognitive disorders and neuroinflammation.
| S-EPMC7066918 | biostudies-literature
Project description:Pyroptosis is a recently characterized inflammatory form of programmed cell death that is thought to be involved in the pathogenesis of perioperative neurocognitive disorders (PND). Elamipretide (SS-31), a mitochondrial-targeted peptide with multiple pharmacological properties, including anti-inflammatory activity, has been demonstrated to protect against many neurological diseases. However, the effect of elamipretide on pyroptosis in PND has not been studied. We established an animal model of PND by performing an exploratory laparotomy on mice under isoflurane anesthesia and examined the effects of elamipretide on cognitive function, synaptic integrity, neuroinflammation, mitochondrial function, and signaling controlling pyroptosis. Our results showed that anesthesia and surgery caused mitochondrial dysfunction and abnormal morphology, activation of canonicalnod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome-caspase-1 dependent pyroptosis, and downregulation of synaptic integrity-related proteins in the hippocampus in aged mice, thus leading to learning and memory deficits in behavioral tests. Remarkably, treatment with the mitochondrial-targeted peptide elamipretide not only had protective effects against mitochondrial dysfunction but also attenuated surgery-induced pyroptosis and cognitive deficits. Our results provide a promising strategy for the treatment of PND involving mitochondrial dysfunction and pyroptosis.
| S-EPMC7439217 | biostudies-literature
Project description:Studies have shown that HIV-infected patients develop neurocognitive disorders characterized by neuronal dysfunction. The lack of productive infection of neurons by HIV suggests that viral and cellular proteins, with neurotoxic activities, released from HIV-1-infected target cells can cause this neuronal deregulation. The viral protein R (Vpr), a protein encoded by HIV-1, has been shown to alter the expression of various important cytokines and inflammatory proteins in infected and uninfected cells; however the mechanisms involved remain unclear. Using a human neuronal cell line, we found that Vpr can be taken up by neurons causing: (i) deregulation of calcium homeostasis, (ii) endoplasmic reticulum-calcium release, (iii) activation of the oxidative stress pathway, (iv) mitochondrial dysfunction and v- synaptic retraction. In search for the cellular factors involved, we performed microRNAs and gene array assays using human neurons (primary cultures or cell line, SH-SY5Y) that we treated with recombinant Vpr proteins. Interestingly, Vpr deregulates the levels of several microRNAs (e.g. miR-34a) and their target genes (e.g. CREB), which could lead to neuronal dysfunctions. Therefore, we conclude that Vpr plays a major role in neuronal dysfunction through deregulating microRNAs and their target genes, a phenomenon that could lead to the development of neurocognitive disorders. Human fetal neurons were chosen to examine the impact of HIV-1 Vpr protein on gene expression
2012-12-07 | E-GEOD-42424 | biostudies-arrayexpress
Project description:Studies have shown that HIV-infected patients develop neurocognitive disorders characterized by neuronal dysfunction. The lack of productive infection of neurons by HIV suggests that viral and cellular proteins, with neurotoxic activities, released from HIV-1-infected target cells can cause this neuronal deregulation. The viral protein R (Vpr), a protein encoded by HIV-1, has been shown to alter the expression of various important cytokines and inflammatory proteins in infected and uninfected cells; however the mechanisms involved remain unclear. Using a human neuronal cell line, we found that Vpr can be taken up by neurons causing: (i) deregulation of calcium homeostasis, (ii) endoplasmic reticulum-calcium release, (iii) activation of the oxidative stress pathway, (iv) mitochondrial dysfunction and v- synaptic retraction. In search for the cellular factors involved, we performed microRNAs and gene array assays using human neurons (primary cultures or cell line, SH-SY5Y) that we treated with recombinant Vpr proteins. Interestingly, Vpr deregulates the levels of several microRNAs (e.g. miR-34a) and their target genes (e.g. CREB), which could lead to neuronal dysfunctions. Therefore, we conclude that Vpr plays a major role in neuronal dysfunction through deregulating microRNAs and their target genes, a phenomenon that could lead to the development of neurocognitive disorders. Using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Vpr) on the expression of miRNAs and mRNAs.
2013-02-12 | E-GEOD-44266 | biostudies-arrayexpress