Ghrelin Attenuates Neuroinflammation and Demyelination in Experimental Autoimmune Encephalomyelitis Involving NLRP3 Inflammasome Signaling Pathway and Pyroptosis

Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system, and conventional treatments have limited efficacy or side effects. Ghrelin, a 28-amino acid octanoylated peptide, has been reported to have neuroprotective effects, including anti-oxidation, anti-inflammation, and anti-apoptosis. Pyroptosis, also called inflammatory cell death, is triggered by overly active inflammasomes and accompanied by the production of numerous cytokines. As immune dysfunction is primarily involved in the pathogenesis of MS, this study aimed to explore the therapeutic effects and precise functional mechanisms of ghrelin against the nod-like receptor protein 3 (NLRP3) inflammasome and pyroptosis in experimental autoimmune encephalomyelitis (EAE). Sprague Dawley rats were immunized with guinea pig spinal cord homogenates and pertussis toxin to develop an EAE model. All rats were randomly divided into four groups: normal control group, EAE group, EAE + ghrelin group, and ghrelin control group. EAE rats showed abnormal behavioral scores and body weight changes. Histologic analysis displayed severe inflammatory infiltration and demyelination in the brain and spinal cord of EAE rats. Ghrelin treatments potently restored these abnormal changes. In addition, the ghrelin-treated EAE group showed significantly downregulated expression of inflammatory cytokines. The expression of proteins involved in the NLRP3 signaling pathway and pyroptosis was decreased as wel...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research

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Publication date: Available online 5 December 2019Source: CellAuthor(s): Chun-Cheih Chao, Cristina Gutiérrez-Vázquez, Veit Rothhammer, Lior Mayo, Michael A. Wheeler, Emily C. Tjon, Stephanie E.J. Zandee, Manon Blain, Kalil Alves de Lima, Maisa C. Takenaka, Julian Avila-Pacheco, Patrick Hewson, Lei Liu, Liliana M. Sanmarco, Davis M. Borucki, Gabriel Z. Lipof, Sunia A. Trauger, Clary B. Clish, Jack P. Antel, Alexandre PratSummaryMetabolism has been shown to control peripheral immunity, but little is known about its role in central nervous system (CNS) inflammation. Through a combination of proteomic, metabolomi...
Source: Cell - Category: Cytology Source Type: research
The U.S. Food and Drug Administration has approved three applications for first generics of Gilenya (fingolimod) capsules for the treatment of relapsing forms of multiple sclerosis (MS) in adult patients. MS is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communication between the brain and other parts of the body.
Source: World Pharma News - Category: Pharmaceuticals Tags: Featured FDA Regulatory Affairs Source Type: news
Conclusion: The downregulation in the expression of QKI-V5 in the blood of patients with CNS-inflammatory-demyelinating-diseases and in the brain and blood of EAE mice is likely caused by a circulating factor and might promote re-myelination by regulation of myelin-associated genes. Key words: QKI variants, Multiple sclerosis (MS), Neuromyelitis optica (NMO), Astrocytes, Demyelination
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
In conclusion, T2D impairs vascular function by dysregulated autophagy. Therefore, autophagy could be a potential target for overcoming diabetic microvascular complications. To What Degree Does Loss of Skeletal Muscle with Age Contribute to Immunosenescence? https://www.fightaging.org/archives/2019/11/to-what-degree-does-loss-of-skeletal-muscle-with-age-contribute-to-immunosenescence/ Sarcopenia, the progressive loss of muscle mass and strength, is characteristic of aging. A perhaps surprisingly large fraction of the losses can be averted by strength training, but there are nonetheless inexorable process...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: De Silvestri A, Capittini C, Mallucci G, Bergamaschi R, Rebuffi C, Pasi A, Martinetti M, Tinelli C Abstract Multiple Sclerosis (MS) displays a heterogeneous clinical onset and progression, which are mostly unpredictable, but demyelination of the central nervous system (CNS) leads to substantial deficits of sensory, motor, autonomic, and neurocognitive functions. Considering all genetic studies on MS, including the advanced genome-wide association studies, the risk linked to HLA alleles remains the highest among other susceptibility genetic variants. However, given the genetic variability of HLA alleles in ...
Source: Disease Markers - Category: Laboratory Medicine Tags: Dis Markers Source Type: research
In this study, we investigated the role of TNFR2 expressed in the oligodendrocyte in the early phase of EAE pathogenesis. We demonstrated that mice with specific ablation of oligodendroglial TNFR2 displayed early onset and higher peak of motor dysfunction when subjected to EAE, in advance of which accelerated infiltration of immune cells was observed as early as 10 days post EAE induction. The immune cell influx was preceded by microglial activation and increased blood brain barrier permeability. Lack of oligodendroglial TNFR2 accelerated the expression of inflammatory cytokines as well as expression and activation of the ...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
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Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
Women have increased prevalence of Th17-mediated autoimmune diseases, including lupus and multiple sclerosis, and severe asthma. While estradiol and progesterone increased IL-17A production in Th17 cells by inhibiting Let7f miRNA expression and increasing IL-23 receptor (IL-23R) expression, it remained unclear how estrogen signaling through the canonical nuclear receptors, estrogen receptor α (ERα) and/or ERβ, regulated this pathway. We hypothesized that estrogen signaling through ERα increased IL-23R expression and IL-17A production from Th17 cells. To test this hypothesis, naïve T cells from W...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study, we investigated the role of TNFR2 expressed in the oligodendrocyte in the early phase of EAE pathogenesis. We demonstrated that mice with specific ablation of oligodendroglial TNFR2 displayed early onset and higher peak of motor dysfunction when subjected to EAE, in advance of which accelerated infiltration of immune cells was observed as early as 10 days post EAE induction. The immune cell influx was preceded by microglial activation and increased blood brain barrier permeability. Lack of oligodendroglial TNFR2 accelerated the expression of inflammatory cytokines as well as expression and activation of the ...
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Tags: Brain Behav Immun Source Type: research
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