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dc.contributor.authorFernández-Arjona, María del Mar
dc.contributor.authorGrondona, Jesús M
dc.contributor.authorFernández-Llebrez, Pedro 
dc.contributor.authorLópez-Ávalos, María Dolores 
dc.date.accessioned2019-10-01T06:51:28Z
dc.date.available2019-10-01T06:51:28Z
dc.date.created2019
dc.date.issued2019-10-01
dc.identifier.urihttps://hdl.handle.net/10630/18498
dc.description.abstractThe sialidase neuraminidase (NA) cleaves terminal sialic acid from glycoproteins and glycolipids. Among its various locations, it is present in the envelope/membrane of some bacteria/viruses (e.g. influenza virus), where it is involved in infectiveness and dispersion. The injection of NA within the brain lateral ventricle represents a model of acute sterile inflammation. The relevance of the toll-like receptors TLR2 and TLR4 (particularly those in microglial cells) in such process was investigated using mouse strains deficient in these receptors. In septofimbria and hypothalamus, IBA1-positive and IL-1β-positive cell counts increased after NA injection in wild type (WT) mice. In TLR4-/- mice such increases were largely abolished, while only slightly affected in TLR2-/- mice. Similarly, the NA-induced expression of IL-1β, TNFα and IL-6 (evaluated by qPCR) was completely blocked in TLR4-/- mice, and only partially reduced in TLR2-/- mice. Microglia was isolated from the three mouse strains and exposed to NA or to specific TLR2 and TLR4 agonists (Pam3CSK4 and LPS respectively) in vitro. NA induced a cytokine response (IL-1β, TNFα and IL-6) in WT microglia, but was unable to do so in TLR4-/- microglia; TLR2 deficiency partially affected the NA-induced microglia response. To investigate if such response of microglial cells to NA was dependent on the sialidase activity of the enzyme, WT microglia was exposed in vitro to NA previously inactivated with heat, or inhibited with two different sialidase inhibitors (oseltamivir phosphate and N-acetyl-2,3-dehydro-2-deoxyneuraminic acid). In all cases, NA- induced microglia activation was dependent on the intact sialidase activity of NA. Therefore, we conclude that NA is able to directly activate microglial cells, mostly through TLR4 receptor and due to its sialidase activity. Accordingly, the inflammatory reaction induced by NA in vivo is partially dependent on TLR2, while TLR4 plays a crucial role.en_US
dc.description.sponsorshipUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.en_US
dc.language.isoengen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectEnzimas víricasen_US
dc.subjectEnzimas microbianasen_US
dc.subjectSistema nervioso - Inflamaciónen_US
dc.subjectExperimentación animalen_US
dc.subject.otherNeuraminidaseen_US
dc.subject.otherNeuroinflammationen_US
dc.subject.otherMicrogliaen_US
dc.subject.otherTLR4en_US
dc.subject.otherTLRsen_US
dc.titleNeuraminidase-induced neuroinflammation is largely dependent on microglial TLR4 receptoren_US
dc.typeinfo:eu-repo/semantics/conferenceObjecten_US
dc.centroFacultad de Cienciasen_US
dc.relation.eventtitle18th National Meeting of the Spanish Society of Neuroscienceen_US
dc.relation.eventplaceSantiago de Compostela (Spain)en_US
dc.relation.eventdate4-6 septiembre 2019en_US


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