0000000000326938

AUTHOR

Seija Lehnardt

showing 4 related works from this author

Expression of Toll-Like Receptors in the Developing Brain

2012

Toll-like receptors (TLR) are key players of the innate and adaptive immune response in vertebrates. The original protein Toll in Drosophila melanogaster regulates both host defense and morphogenesis during development. Making use of real-time PCR, in situ hybridization, and immunohistochemistry we systematically examined the expression of TLR1-9 and the intracellular adaptor molecules MyD88 and TRIF during development of the mouse brain. Expression of TLR7 and TLR9 in the brain was strongly regulated during different embryonic, postnatal, and adult stages. In contrast, expression of TLR1-6, TLR8, MyD88, and TRIF mRNA displayed no significant changes in the different phases of brain develop…

AgingGene Expressionlcsh:MedicineMiceMolecular Cell BiologyMorphogenesislcsh:ScienceReceptorImmune ResponseRegulation of gene expressionMultidisciplinaryNeocortexToll-Like ReceptorsBrainGene Expression Regulation DevelopmentalAcquired immune systemInnate ImmunityCell biologyInfectious Diseasesmedicine.anatomical_structureMedicineResearch ArticleImmunologyCentral nervous systemMorphogenesisIn situ hybridizationBiologyMolecular GeneticsImmune ActivationDevelopmental NeuroscienceGeneticsmedicineAnimalsHumansRNA MessengerBiologyImmunity to Infectionslcsh:RImmunityComputational BiologyImmune DefenseAxonsHEK293 CellsTRIFImmune SystemCellular NeuroscienceImmunologyClinical Immunologylcsh:QTranscriptomeDevelopmental BiologyNeurosciencePLoS ONE
researchProduct

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

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

In Vivo Imaging of Partially Reversible Th17 Cell-Induced Neuronal Dysfunction in the Course of Encephalomyelitis

2010

SummaryNeuronal damage in autoimmune neuroinflammation is the correlate for long-term disability in multiple sclerosis (MS) patients. Here, we investigated the role of immune cells in neuronal damage processes in animal models of MS by monitoring experimental autoimmune encephalomyelitis (EAE) by using two-photon microscopy of living anaesthetized mice. In the brainstem, we detected sustained interaction between immune and neuronal cells, particularly during disease peak. Direct interaction of myelin oligodendrocyte glycoprotein (MOG)-specific Th17 and neuronal cells in demyelinating lesions was associated with extensive axonal damage. By combining confocal, electron, and intravital microsc…

Cell signalingPathologymedicine.medical_specialtyEncephalomyelitis Autoimmune ExperimentalEncephalomyelitisImmunologyApoptosisCell CommunicationBiologyReceptors N-Methyl-D-AspartateMyelin oligodendrocyte glycoproteinMiceImmune systemCell MovementmedicineAnimalsImmunology and AllergyNeuroinflammationCells CulturedNeuronsMultiple sclerosisExperimental autoimmune encephalomyelitisInterleukin-17T-Lymphocytes Helper-Inducermedicine.diseaseAxonsCell biologyMice Inbred C57BLInfectious Diseasesnervous systemSynapsesbiology.proteinCalciumIntravital microscopyImmunity
researchProduct