دورية أكاديمية
NADPH oxidase 2 as a potential therapeutic target for protection against cognitive deficits following systemic inflammation in mice.
| العنوان: | NADPH oxidase 2 as a potential therapeutic target for protection against cognitive deficits following systemic inflammation in mice. |
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| المؤلفون: | Huang WY; Institute of Basic Medicine, College of Medicine, National Cheng-Kung University, Tainan, Taiwan; Pediatrics of Kung-Ten General Hospital, Taichung City, Taiwan., Liu KH; Inflammation Research & Drug Development Center, Changhua Christian Hospital, Changhua, Taiwan., Lin S; Inflammation Research & Drug Development Center, Changhua Christian Hospital, Changhua, Taiwan., Chen TY; Inflammation Research & Drug Development Center, Changhua Christian Hospital, Changhua, Taiwan., Tseng CY; Inflammation Research & Drug Development Center, Changhua Christian Hospital, Changhua, Taiwan., Chen HY; Inflammation Research & Drug Development Center, Changhua Christian Hospital, Changhua, Taiwan., Wu HM; Inflammation Research & Drug Development Center, Changhua Christian Hospital, Changhua, Taiwan; Department of Neurology, Changhua Christian Hospital, Changhua City, Taiwan; Institute of Acupuncture, School of Chinese Medicine, China Medical University, Taichung City, Taiwan. Electronic address: 18288@cch.org.tw., Hsu KS; Institute of Basic Medicine, College of Medicine, National Cheng-Kung University, Tainan, Taiwan. Electronic address: richard@mail.ncku.edu.tw. |
| المصدر: | Brain, behavior, and immunity [Brain Behav Immun] 2020 Feb; Vol. 84, pp. 242-252. Date of Electronic Publication: 2019 Dec 10. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8800478 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2139 (Electronic) Linking ISSN: 08891591 NLM ISO Abbreviation: Brain Behav Immun Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2000- > : Amsterdam : Elsevier Original Publication: San Diego : Academic Press, [c1987- |
| مواضيع طبية MeSH: | Cognitive Dysfunction*/drug therapy , Cognitive Dysfunction*/etiology , Inflammation*/complications , NADPH Oxidase 2*/metabolism , Onium Compounds*/pharmacology , Onium Compounds*/therapeutic use, Animals ; Chronic Disease ; Enzyme Activation/drug effects ; Enzyme Inhibitors/pharmacology ; Enzyme Inhibitors/therapeutic use ; Mice ; Mice, Inbred C57BL ; Microglia/drug effects ; Microglia/pathology ; Reactive Oxygen Species |
| مستخلص: | Background: Research indicates that sepsis increases the risk of developing cognitive impairment. After systemic inflammation, a corresponding activation of microglia is rapidly induced in the brain, and multiple neurotoxic factors, including inflammatory mediators (e.g., cytokines) and reactive oxygen species (e.g., superoxide), are also released that contribute to neuronal injury. NADPH oxidase (NOX) enzymes play a vital role in microglial activation through the generation of superoxide anions. We hypothesized that NOX isoforms, particularly NOX2, could exhibit remarkable abilities in developing cognitive deficits induced by systemic inflammation. Methods: Mice with deficits of NOX2 organizer p47phox (p47 phox -/- ) and wild-type (WT) mice treated with the NOX inhibitor diphenyleneiodonium (DPI) were used in this study. Intraperitoneal lipopolysaccharide (LPS) injection was used to induce systemic inflammation. Spatial learning and memory were compared among treatment groups using the radial arm maze task. Brain tissues were collected for evaluating the transcript levels of proinflammatory cytokines, whereas immunofluorescence staining and immunoblotting were conducted to determine the percentage of activated glia (microglia and astroglia) and damaged neurons and the expression of synaptic proteins and BDNF. Results: Cognitive impairment induced by systemic inflammation was significantly attenuated in the p47 phox -/- mice compared to that in the WT mice. The p47 phox -/- mice exhibited reduced microglial and astroglial activation and neuronal damage and attenuated the induction of multiple proinflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and CCL2. Similar to that observed in the p47 phox -/- mice, the administration of DPI significantly attenuated the cognitive impairment, reduced the glial activation and brain cytokine concentrations, and restored the expression of postsynaptic proteins (PSD-95) and BDNF in neurons and astrocytes, compared to those in the vehicle-treated controls within 10 days after LPS injection. Conclusions: This study clearly demonstrates that NOX2 contributes to glial activation with subsequent reduction in the expression of BDNF, synaptic dysfunction, and cognitive deficits after systemic inflammation in an LPS-injected mouse model. Our results provide evidence that NOX2 might be a promising pharmacological target that could be used to protect against synaptic dysregulation and cognitive impairment following systemic inflammation. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2019 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Brain-derived neurotrophic factor; Cognition; Cytokine; Diphenyleneiodonium; Lipopolysaccharide; Neuroinflammation; Nicotinamide adenine dinucleotide phosphate oxidase; Sepsis |
| المشرفين على المادة: | 0 (Enzyme Inhibitors) 0 (Onium Compounds) 0 (Reactive Oxygen Species) 6HJ411TU98 (diphenyleneiodonium) EC 1.6.3.- (NADPH Oxidase 2) |
| تواريخ الأحداث: | Date Created: 20191217 Date Completed: 20210309 Latest Revision: 20210309 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.bbi.2019.12.006 |
| PMID: | 31841660 |
| قاعدة البيانات: | MEDLINE |
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