Transgenic models to assess the pathogenic actions of cytokines in the central nervous system

Campbell, Iain L.; Stalder, Anna K.; Chiang, C S; Bellinger, R; Heyser, Charles J.; Steffensen, Scott C.; Masliah, Eliezer; Powell, Henry C.; Gold, Lisa; Henriksen, Steven J.; Siggins, George R.

doi:10.1038/sj.mp.4000225

Cited by 83 publications

(51 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…IL-6 has neurotrophic and neuroprotective effects and can increase blood-brain barrier permeability [33]. A high level of IL-6 leads to progressive neurological disorders with neurodegeneration and cognitive decline [34]. The higher level of cerebrospinal fluid IL-8 seen in this study is consistent with the fact that CNS viral infection might induce proliferation of microglia and astrocytes, resulting in the release of IL-8 [35].…”

Section: Discussionsupporting

confidence: 76%

Coronavirus Infections in the Central Nervous System and Respiratory Tract Show Distinct Features in Hospitalized Children

et al. 2016

View full text Add to dashboard Cite

Background/Aims: Coronavirus (CoV) infections induce respiratory tract illnesses and central nervous system (CNS) diseases. We aimed to explore the cytokine expression profiles in hospitalized children with CoV-CNS and CoV-respiratory tract infections. Methods: A total of 183 and 236 hospitalized children with acute encephalitis-like syndrome and respiratory tract infection, respectively, were screened for anti-CoV IgM antibodies. The expression profiles of multiple cytokines were determined in CoV-positive patients. Results: Anti-CoV IgM antibodies were detected in 22/183 (12.02%) and 26/236 (11.02%) patients with acute encephalitis-like syndrome and respiratory tract infection, respectively. Cytokine analysis revealed that the level of serum granulocyte colony-stimulating factor (G-CSF) was significantly higher in both CoV-CNS and CoV-respiratory tract infection compared with healthy controls. Additionally, the serum level of granulocyte macrophage colony-stimulating factor (GM-CSF) was significantly higher in CoV-CNS infection than in CoV-respiratory tract infection. In patients with CoV-CNS infection, the levels of IL-6, IL-8, MCP-1, and GM-CSF were significantly higher in their cerebrospinal fluid samples than in matched serum samples. Conclusion: To the best of our knowledge, this is the first report showing a high incidence of CoV infection in hospitalized children, especially with CNS illness. The characteristic cytokine expression profiles in CoV infection indicate the importance of host immune response in disease progression.

show abstract

Section: Discussionsupporting

confidence: 76%

Coronavirus Infections in the Central Nervous System and Respiratory Tract Show Distinct Features in Hospitalized Children

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In the symptomatic transgenic mice that exhibit distinct neurological disorders, 20 striking differences in the cerebral chemokine gene expression were observed with dominance of specific chemokine genes. Thus, in GFAP-IL3 mice, C10 and the C10-related chemokine gene expression was most prominent.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the objective of the current study was to compare the regulation of chemokine gene expression in a number of different models for CNS inflammation which included EAE and recently developed transgenic mice with astrocyte-targeted expression of the proinflammatory cytokines IL-3, 17 IL-6, 18 or IFN␣. 19 These transgenic mice develop distinct neuroinflammatory disorders 20 and are therefore useful tools for better understanding the role of chemokines in leukocyte migration to the CNS. The GFAP-IL6 mice exhibit diffuse inflammation in the brain and have some perivascular mononuclear cell accumulation, mainly with B lymphocytes, but little or no parenchymal leukocyte accumulation.…”

mentioning

confidence: 99%

C10 Is a Novel Chemokine Expressed in Experimental Inflammatory Demyelinating Disorders that Promotes Recruitment of Macrophages to the Central Nervous System

Asensio

Laßmann

Pagenstecher

et al. 1999

The American Journal of Pathology

View full text Add to dashboard Cite

Chemokines may be important in the control of leukocytosis in inflammatory disorders of the central nervous system. We studied cerebral chemokine expression during the evolution of diverse neuroinflammatory disorders in transgenic mice with astrocyte glial fibrillary acidic protein-targeted expression of the cytokines IL-3 , IL-6 , or IFN-␣ and in mice with experimental autoimmune encephalomyelitis. Distinct chemokine gene expression patterns were observed in the different central nervous system inflammatory models that may determine the phenotype and perhaps the functions of the leukocytes that traffic into the brain. Notably , high expression of C10 and C10-related genes was found in the cerebellum and spinal cord of GFAP-IL3 mice with inflammatory demyelinating disease and in mice with experimental autoimmune encephalomyelitis. In both these neuroinflammatory models , C10 RNA and protein expressing cells were predominantly macrophage/microglia and foamy macrophages present within demyelinating lesions as well as in perivascular infiltrates and meninges. Intracerebroventricular injection of recombinant C10 protein promoted the recruitment of large numbers of Mac-1 ؉ cells and, to a much lesser extent , CD4؉ lymphocytes into the meninges , choroid plexus , ventricles , and parenchyma of the brain. Thus , C10 is a prominent chemokine expressed in the central nervous system in experimental inflammatory demyelinating disease that, we show , also acts as a potent chemotactic factor for the migration of these leukocytes to the brain. (Am J Pathol 1999, 154:1181-1191)

show abstract

“…As high levels of IL-6 have also been reported to inhibit pro-inflammatory TNF-a (Petersen and Pedersen, 2005), overexpression of IL-6 is not necessarily in contrast with the observed downregulation of TNF-a and could have a role in RTT etiopathology. Indeed, exposure to high levels of IL-6, as observed during normal aging, in certain neurodegenerative diseases and in mice overexpressing IL-6 in glial cells, results in neuropathological and functional alterations, including decreased synaptic plasticity and impaired neurogenesis (Bellinger et al, 1995;Campbell, 1998;Campbell et al, 1997Campbell et al, , 1998Godbout and Johnson, 2004;Heyser et al, 1997;Vallieres et al, 2002;Vereyken et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Modulation of RhoGTPases Improves the Behavioral Phenotype and Reverses Astrocytic Deficits in a Mouse Model of Rett Syndrome

Filippis

Fabbri

Simone

et al. 2011

Neuropsychopharmacol

109

View full text Add to dashboard Cite

RhoGTPases are crucial molecules in neuronal plasticity and cognition, as confirmed by their role in non-syndromic mental retardation. Activation of brain RhoGTPases by the bacterial cytotoxic necrotizing factor 1 (CNF1) reshapes the actin cytoskeleton and enhances neurotransmission and synaptic plasticity in mouse brains. We evaluated the effects of a single CNF1 intracerebroventricular inoculation in a mouse model of Rett syndrome (RTT), a rare neurodevelopmental disorder and a genetic cause of mental retardation, for which no effective therapy is available. Fully symptomatic MeCP2-308 male mice were evaluated in a battery of tests specifically tailored to detect RTT-related impairments. At the end of behavioral testing, brain sections were immunohistochemically characterized. Magnetic resonance imaging and spectroscopy (MRS) were also applied to assess morphological and metabolic brain changes. The CNF1 administration markedly improved the behavioral phenotype of MeCP2-308 mice. CNF1 also dramatically reversed the evident signs of atrophy in astrocytes of mutant mice and restored wt-like levels of this cell population. A partial rescue of the overexpression of IL-6 cytokine was also observed in RTT brains. CNF1-induced brain metabolic changes detected by MRS analysis involved markers of glial integrity and bioenergetics, and point to improved mitochondria functionality in CNF1-treated mice. These results clearly indicate that modulation of brain RhoGTPases by CNF1 may constitute a totally innovative therapeutic approach for RTT and, possibly, for other disorders associated with mental retardation.

show abstract

Transgenic models to assess the pathogenic actions of cytokines in the central nervous system

Cited by 83 publications

References 5 publications

Coronavirus Infections in the Central Nervous System and Respiratory Tract Show Distinct Features in Hospitalized Children

Coronavirus Infections in the Central Nervous System and Respiratory Tract Show Distinct Features in Hospitalized Children

C10 Is a Novel Chemokine Expressed in Experimental Inflammatory Demyelinating Disorders that Promotes Recruitment of Macrophages to the Central Nervous System

Modulation of RhoGTPases Improves the Behavioral Phenotype and Reverses Astrocytic Deficits in a Mouse Model of Rett Syndrome

Contact Info

Product

Resources

About