0000000000019032

AUTHOR

Karen Rosenberger

showing 3 related works from this author

Elevation in type I interferons inhibits HCN1 and slows cortical neuronal oscillations

2014

Central nervous system (CNS) inflammation involves the generation of inducible cytokines such as interferons (IFNs) and alterations in brain activity, yet the interplay of both is not well understood. Here, we show that in vivo elevation of IFNs by viral brain infection reduced hyperpolarization-activated currents (Ih) in cortical pyramidal neurons. In rodent brain slices directly exposed to type I IFNs, the hyperpolarization-activated cyclic nucleotide (HCN)-gated channel subunit HCN1 was specifically affected. The effect required an intact type I receptor (IFNAR) signaling cascade. Consistent with Ih inhibition, IFNs hyperpolarized the resting membrane potential, shifted the resonance fre…

MalePatch-Clamp TechniquesPotassium Channelsmedicine.medical_treatmentNeocortexInbred C57BLchemistry.chemical_compoundMiceReceptorsHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsReceptors InterferonMembrane potentialCerebral CortexNeuronsBlottingElectroencephalographyImmunohistochemistryCytokinemedicine.anatomical_structureInterferon Type IInterferonCytokinesSignal transductionWesternmedicine.drugSignal TransductionCognitive NeuroscienceCentral nervous systemBlotting WesternElectrophysiological ProcessesBiologyReal-Time Polymerase Chain ReactionTransfectionCellular and Molecular NeuroscienceCyclic nucleotidemedicineAnimalsHumansComputer SimulationIon channelNeuroinflammationInterferon-betaElectrophysiological PhenomenaRatsMice Inbred C57BLHEK293 CellschemistryNerve NetNeuroscienceInterferon type I
researchProduct

MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4

2015

A body of experimental evidence suggests that T cells mediate neuroprotection following CNS injury; however, the antigen specificity of these T cells and how they mediate neuroprotection are unknown. Here, we have provided evidence that T cell-mediated neuroprotection after CNS injury can occur independently of major histocompatibility class II (MHCII) signaling to T cell receptors (TCRs). Using two murine models of CNS injury, we determined that damage-associated molecular mediators that originate from injured CNS tissue induce a population of neuroprotective, IL-4-producing T cells in an antigen-independent fashion. Compared with wild-type mice, IL-4-deficient animals had decreased functi…

CD4-Positive T-LymphocytesCancer ResearchMAP Kinase Signaling SystemPopulationReceptors Antigen T-CellInflammationBiologyNeuroprotectionMiceAntigenClinical investigationAnimalsMedicineExtracellular Signal-Regulated MAP KinaseseducationReceptorInterleukin 4Mice Knockouteducation.field_of_studybusiness.industryT-cell receptorHistocompatibility Antigens Class IINeurodegenerative DiseasesGeneral MedicineAxonsCell biologyBrain InjuriesMyeloid Differentiation Factor 88Immunologybiology.proteinInterleukin-4medicine.symptomFunction and Dysfunction of the Nervous SystemCorrigendumbusinessProto-Oncogene Proteins c-aktResearch ArticleNeurotrophinJournal of Clinical Investigation
researchProduct

An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration

2011

Activation of innate immune receptors by host-derived factors exacerbates CNS damage, but the identity of these factors remains elusive. We uncovered an unconventional role for the microRNA let-7, a highly abundant regulator of gene expression in the CNS, in which extracellular let-7 activates the RNA-sensing Toll-like receptor (TLR) 7 and induces neurodegeneration through neuronal TLR7. Cerebrospinal fluid (CSF) from individuals with Alzheimer’s disease contains increased amounts of let-7b, and extracellular introduction of let-7b into the CSF of wild-type mice by intrathecal injection resulted in neurodegeneration. Mice lacking TLR7 were resistant to this neurodegenerative effect, but thi…

Cell signalingApoptosisElectrophoretic Mobility Shift AssayBiologyReal-Time Polymerase Chain ReactionMiceAlzheimer DiseasemicroRNAExtracellularmedicineAnimalsHumansReceptorIn Situ HybridizationMice KnockoutNeuronsToll-like receptorMembrane GlycoproteinsMicroscopy ConfocalInnate immune systemGeneral NeuroscienceNeurodegenerationBrainvirus diseasesTLR7medicine.diseaseImmunohistochemistryMice Inbred C57BLMicroRNAsHEK293 CellsToll-Like Receptor 7Nerve DegenerationCancer researchSignal TransductionNature Neuroscience
researchProduct