2025
Disease modification upon 2 weeks of tofacitinib treatment in a mouse model of chronic epilepsy
Hoffman O, Koehler J, Espina J, Patterson A, Gohar E, Coleman E, Schoenike B, Espinosa-Garcia C, Paredes F, Varvel N, Dingledine R, Maguire J, Roopra A. Disease modification upon 2 weeks of tofacitinib treatment in a mouse model of chronic epilepsy. Science Translational Medicine 2025, 17: eadt0527. PMID: 40106581, DOI: 10.1126/scitranslmed.adt0527.Peer-Reviewed Original ResearchConceptsTranscriptome dataJanus kinase/signal transducer and activatorKinase/signal transducer and activatorReverse cognitive deficitsJAK/STAT activationJAK/STAT3 signalingChronic epilepsyModel of temporal lobe epilepsySpontaneous seizuresMouse models of chronic epilepsyMouse modelCognitive deficitsSpatial memoryTransient inductionTemporal lobe epilepsyMouse model of temporal lobe epilepsyModel of chronic epilepsyLobectomy samplesDisease modificationTreat symptomsLobe epilepsyWhole tissueDrug treatmentEpileptogenic insultTofacitinib treatmentDirect quantification of cell type-specific proteins using Luminex assays with TurboID-labeled cells and tissues
Bitarafan S, Tobin B, Espinosa-Garcia C, Rangaraju S, Wood L. Direct quantification of cell type-specific proteins using Luminex assays with TurboID-labeled cells and tissues. Methods In Cell Biology 2025 DOI: 10.1016/bs.mcb.2025.03.001.Peer-Reviewed Original ResearchCell type-specific proteinsBiotinylation of proteinsCell type-specificType-specific proteinsCell type contributionsCell culturesEfficient biotinylationTagged proteinsLabeling proteomicsPhospho-proteinsProteome labelingCellular functionsMulti-cellular systemsProteomic investigationsType-specificProteinIn vivo settingMouse linesCellsViral constructsTransgenic mouse linesTurboIDProteomicsImmunoassay platformImmunoprecipitation
2024
Neuroinflammatory Stress Exerts Distinct Proteomic Effects on Soma, Synapses and Mitochondria in Excitatory Neurons
Espinosa‐Garcia C, Srivastava U, Kumar P, Tobin B, Xiao H, Cheng L, Bagchi P, Duong D, Seyfried N, Faundez V, Wood L, Rangaraju S. Neuroinflammatory Stress Exerts Distinct Proteomic Effects on Soma, Synapses and Mitochondria in Excitatory Neurons. Alzheimer's & Dementia 2024, 20: e090723. PMCID: PMC11710382, DOI: 10.1002/alz.090723.Peer-Reviewed Original ResearchProteomic effectsLabel-free quantitative mass spectrometryCytoskeleton-related proteinsAlzheimer's disease pathogenesisProteome in vivoIncreased aerobic respirationCellular signaling pathwaysQuantitative mass spectrometryDisease pathogenesisCytoskeleton organizationSubcellular compartmentsOxidoreductase activitySynaptic vesiclesProteomic approachAerobic respirationBiological pathwaysNeuroinflammatory stressSignaling pathwaySynapse-related proteinsMAPK signalingMetabolic processesDifferential centrifugationMitochondriaSomatodendritic compartmentRegulating activityKv1.3 regulation of brain immune function in vitro and in vivo
Bowen C, Nguyen H, Lin Y, Bagchi P, Natu A, Xiao H, Espinosa‐Garcia C, Kumar P, Wulff H, Seyfried N, Rangaraju S. Kv1.3 regulation of brain immune function in vitro and in vivo. Alzheimer's & Dementia 2024, 20: e093042. PMCID: PMC11709668, DOI: 10.1002/alz.093042.Peer-Reviewed Original ResearchProtein processingN-terminusProximity-based proteomicsProtein-protein interactomePDZ-binding motifPDZ-binding domainPlasma membrane proteinsDeletion in vivoJurkat T cellsT cellsKO miceBiotin ligaseCMV-Cre miceRNA-seqTrafficking proteinsBiotinylated proteinsTranscriptome levelC-terminusMembrane proteinsInteractorsMicroglial signatureImmune signalingPlasma membraneLPS stimulationDifferential expressionATR-FTIR spectroscopy to evaluate serum protein expression in a murine cerebral ischemia model
Montes-Narváez O, García-Juárez M, Beltrán-Pérez G, Espinosa-García C, González-Flores O, Delgado-Macuil R. ATR-FTIR spectroscopy to evaluate serum protein expression in a murine cerebral ischemia model. Spectrochimica Acta Part A Molecular And Biomolecular Spectroscopy 2024, 326: 125261. PMID: 39395276, DOI: 10.1016/j.saa.2024.125261.Peer-Reviewed Original ResearchEditorial: Immune system mechanisms impacting the onset of epilepsy and spontaneous seizures
Espinosa-Garcia C, Bahramnejad E, Li Y. Editorial: Immune system mechanisms impacting the onset of epilepsy and spontaneous seizures. Frontiers In Molecular Neuroscience 2024, 17: 1487871. PMID: 39318421, PMCID: PMC11420127, DOI: 10.3389/fnmol.2024.1487871.Peer-Reviewed Original ResearchProximity Labeling Proteomics Reveals Kv1.3 Potassium Channel Immune Interactors in Microglia
Bowen C, Nguyen H, Lin Y, Bagchi P, Natu A, Espinosa-Garcia C, Werner E, Kumari R, Brandelli A, Kumar P, Tobin B, Wood L, Faundez V, Wulff H, Seyfried N, Rangaraju S. Proximity Labeling Proteomics Reveals Kv1.3 Potassium Channel Immune Interactors in Microglia. Molecular & Cellular Proteomics 2024, 23: 100809. PMID: 38936775, PMCID: PMC11780389, DOI: 10.1016/j.mcpro.2024.100809.Peer-Reviewed Original ResearchDisease-associated microgliaPDZ-binding domainImmune signaling proteinsInflammatory responseProinflammatory signaling moleculesInhibition of Kv1.3Resident immune cellsSignaling proteinsKv1.3 potassium channelsC-terminusC-terminal PDZ-binding domainMicroglia transitionTLR4-mediated activationLipopolysaccharide-induced inflammatory responseKv1.3 blockadeImmune cellsPotential interacting proteinsInflammatory statePotassium channelsInflammatory contextKv1.3Flux of potassium ionsTLR4-induced inflammatory responsesFlow cytometryGlycolytic responseNative-state proteomics of Parvalbumin interneurons identifies unique molecular signatures and vulnerabilities to early Alzheimer’s pathology
Kumar P, Goettemoeller A, Espinosa-Garcia C, Tobin B, Tfaily A, Nelson R, Natu A, Dammer E, Santiago J, Malepati S, Cheng L, Xiao H, Duong D, Seyfried N, Wood L, Rowan M, Rangaraju S. Native-state proteomics of Parvalbumin interneurons identifies unique molecular signatures and vulnerabilities to early Alzheimer’s pathology. Nature Communications 2024, 15: 2823. PMID: 38561349, PMCID: PMC10985119, DOI: 10.1038/s41467-024-47028-7.Peer-Reviewed Original ResearchConceptsBiotinylation of proteinsAlzheimer's diseasePre-synaptic defectsDecreased mTOR signalingAD pathogenesisAD riskCytoskeletal disruptionProteomic alterationsTranslational activityMolecular insightsMTOR signalingProteomic findingsProteomicsProteomic signatureMolecular signaturesProteinOver-representedProgressive neuropathologyAlzheimer pathologyMouse modelPV-INsParvalbumin interneuronsMitochondriaAssociated with cognitive declineFast-spiking parvalbumin interneurons
2023
Immune regulatory roles for Kv1.3 channels in Microglia in Alzheimer’s Disease
Bowen C, Lin Y, Zeng H, Nguyen H, Xiao H, Kumar P, Duong D, Espinosa‐Garcia C, Wulff H, Seyfried N, Rangaraju S. Immune regulatory roles for Kv1.3 channels in Microglia in Alzheimer’s Disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.078851.Peer-Reviewed Original ResearchKv1.3 blockadeKv1.3 channelsKv1.3 blockersMouse model of AD pathologyBlockade of Kv1.3Immune regulatory roleWestern blottingAlzheimer's diseaseCMV-Cre miceChannels in vitroPDZ-binding motifPlasma membrane proteinsInhibition in vivoCell type-specificPharmacological blockadeOlder 5XFAD miceCMV-CreFunction of microgliaChannel abundanceKv1.3Mouse modelBiotin ligaseFlow cytometryTrafficking proteinsBiotinylated proteinsAge‐Dependent Changes in Perineuronal Nets and Associated Parvalbumin Interneurons in the 5xFAD Amyloidosis Mouse Model
Nelson R, Rangaraju S, Rayaprolu S, Kumar P, Espinosa‐Garcia C, Xiao H. Age‐Dependent Changes in Perineuronal Nets and Associated Parvalbumin Interneurons in the 5xFAD Amyloidosis Mouse Model. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.083101.Peer-Reviewed Original ResearchPV+ neuronsWild typePerineuronal netsAlzheimer's diseaseAD-like pathologyCo-localizationMouse modelAmyloid-betaFast-spiking interneuronsEarly amyloidosisRegulate synaptic transmissionSynaptic maintenanceExtracellular matrix structurePlaque proximityAge-dependent mannerMonths of agePhysiological roleImmunofluorescence microscopyNeuronal roleNeurodegenerative diseasesParvalbumin-positiveParvalbumin interneuronsAge-dependent changesSynaptic transmissionProximal dendritesProfound seizure suppression and disease modification by targeting JAK1, a key driver of a pro-epileptogenic gene network.
Hoffman OR, Patterson A, Gohar E, Coleman E, Schoenike B, Espinosa-Garcia C, Paredes F, Dingledine R, Maguire J, Roopra AS. Profound seizure suppression and disease modification by targeting JAK1, a key driver of a pro-epileptogenic gene network. BioRxiv 2023 PMID: 37662337, DOI: 10.1101/2023.08.07.552299.Peer-Reviewed Original ResearchPROGESTERONE TREATMENT RESTORES NORMAL BLOOD-BRAIN BARRIER FUNCTION IN A RAT MODEL OF CHRONIC CEREBRAL HYPOPERFUSION
Espadín M, Espinosa-Garcia C, Cervantes J, Gomez-Gonzalez B, De La Brena G. PROGESTERONE TREATMENT RESTORES NORMAL BLOOD-BRAIN BARRIER FUNCTION IN A RAT MODEL OF CHRONIC CEREBRAL HYPOPERFUSION. IBRO Neuroscience Reports 2023, 15: s399-s400. DOI: 10.1016/j.ibneur.2023.08.761.Peer-Reviewed Original ResearchEditorial: Environmental effect on neuroinflammation and neurodegeneration, volume II
Sarkar S, Rangaraju S, Espinosa-Garcia C, Langley M. Editorial: Environmental effect on neuroinflammation and neurodegeneration, volume II. Frontiers In Cellular Neuroscience 2023, 17: 1269180. PMID: 37636587, PMCID: PMC10455926, DOI: 10.3389/fncel.2023.1269180.Peer-Reviewed Original ResearchNative-state proteomics of Parvalbumin interneurons identifies novel molecular signatures and metabolic vulnerabilities to early Alzheimer's disease pathology.
Kumar P, Goettemoeller AM, Espinosa-Garcia C, Tobin BR, Tfaily A, Nelson RS, Natu A, Dammer EB, Santiago JV, Malepati S, Cheng L, Xiao H, Duong D, Seyfried NT, Wood LB, Rowan MJ, Rangaraju S. Native-state proteomics of Parvalbumin interneurons identifies novel molecular signatures and metabolic vulnerabilities to early Alzheimer's disease pathology. BioRxiv 2023 PMID: 37292756, DOI: 10.1101/2023.05.17.541038.Peer-Reviewed Original Research
2022
Preclinical development of an EP2 antagonist for post-seizure cognitive deficits
Varvel N, Amaradhi R, Espinosa-Garcia C, Duddy S, Franklin R, Banik A, Alemán-Ruiz C, Blackmer-Raynolds L, Wang W, Honore T, Ganesh T, Dingledine R. Preclinical development of an EP2 antagonist for post-seizure cognitive deficits. Neuropharmacology 2022, 224: 109356. PMID: 36460083, PMCID: PMC9894535, DOI: 10.1016/j.neuropharm.2022.109356.Peer-Reviewed Original ResearchConceptsCognitive deficitsStatus epilepticusY-maze performanceInvestigational new drugEP2 antagonistComorbidities of epilepsyReduced delayed mortalityY-mazeCognitive comorbiditiesBlood-brain barrier leakageDays of oral administrationCOX-2 inductionSigns of toxicityDeficitsIn vitro studiesEP2 receptorReceptor modulatorsDose linearityProstaglandin E2Neuronal injuryPreclinical developmentOral administrationPreventive treatmentHistopathological signsCyclooxygenase-2
2021
Sleep Disruption Worsens Seizures: Neuroinflammation as a Potential Mechanistic Link
Bonilla-Jaime H, Zeleke H, Rojas A, Espinosa-Garcia C. Sleep Disruption Worsens Seizures: Neuroinflammation as a Potential Mechanistic Link. International Journal Of Molecular Sciences 2021, 22: 12531. PMID: 34830412, PMCID: PMC8617844, DOI: 10.3390/ijms222212531.Peer-Reviewed Original ResearchConceptsObstructive sleep apneaSleep deprivationAnti-epileptic drugsEpilepsy-related mortalitySudden unexpected deathPotential mechanistic linkSleep apneaImprove quality of lifeWorsen neurodegenerationDaytime sleepinessDisease progressionSeizure frequencySeizure activityNocturnal seizuresSide effectsQuality of lifeUnexpected deathEpileptic brainSeizuresEpilepsy patientsPoor sleep qualityEpilepsyNeuroinflammationSleep disturbanceMechanistic linkImpact of Stress on Epilepsy: Focus on Neuroinflammation—A Mini Review
Espinosa-Garcia C, Zeleke H, Rojas A. Impact of Stress on Epilepsy: Focus on Neuroinflammation—A Mini Review. International Journal Of Molecular Sciences 2021, 22: 4061. PMID: 33920037, PMCID: PMC8071059, DOI: 10.3390/ijms22084061.Peer-Reviewed Original ResearchConceptsImpact of stressChronic stressPsychiatric comorbidityPsychiatric comorbiditiesStressor durationDepressive stateAcute stressPoor quality of lifeBrain damageSeizure occurrencePreclinical researchSeizure triggersOutcome severityDisordersEpilepsy outcomeEpilepsy patientsRecurrent seizuresEpilepsyNeurological disordersQuality of lifeSeizuresDeleterious impactDepressionComorbidityProgesterone Modulates Mitochondrial Functions in Human Glioblastoma Cells
Atif F, Yousuf S, Espinosa-Garcia C, Stein D. Progesterone Modulates Mitochondrial Functions in Human Glioblastoma Cells. Molecular Neurobiology 2021, 58: 3805-3816. PMID: 33847913, DOI: 10.1007/s12035-021-02382-1.Peer-Reviewed Original ResearchConceptsExtracellular acidification rateEffects of P4Glioblastoma multiformeGlioblastoma multiforme cell linesGlioblastoma multiforme cellsCell linesInhibitory effectDecreased tumor sizeSuperoxide radical generationMitochondrial functionDose-dependent inhibitory effectOxygen consumption rateTime-response studiesMitochondrial respirationHuman glioblastoma multiformeMitochondrial stress testSpread of glioblastoma multiformeCompared to controlsTumor sizeConcentrations of P4Human glioblastoma cellsModulate mitochondrial functionNonmitochondrial oxygen consumptionMaximum inhibitory effectDose response
2020
Peripheral Myeloid Cell EP2 Activation Contributes to the Deleterious Consequences of Status Epilepticus
Varvel N, Espinosa-Garcia C, Hunter-Chang S, Chen D, Biegel A, Hsieh A, Blackmer-Raynolds L, Ganesh T, Dingledine R. Peripheral Myeloid Cell EP2 Activation Contributes to the Deleterious Consequences of Status Epilepticus. Journal Of Neuroscience 2020, 41: 1105-1117. PMID: 33293358, PMCID: PMC7880294, DOI: 10.1523/jneurosci.2040-20.2020.Peer-Reviewed Original ResearchConceptsBlood-brain barrierImmune myeloid cellsEP2 receptorInnate immune cellsStatus epilepticusEP2 antagonismProstaglandin EP2 receptorBlood-borne monocytesMyeloid cellsImmune cellsConsequences of seizuresBrain infiltrationInflammatory cytokinesFormation of inflammatory cytokinesConditional KOInflammatory responsePeripheral innate immune cellsActivation of EP2 receptorsQuality of lifeEP2 receptor antagonistRecruitment of blood-borne monocytesSerum albumin levelPeripheral immune cellsConsequences of status epilepticusHippocampal IL-6Stroke-Induced Peripheral Immune Dysfunction in Vitamin D–Deficient Conditions: Modulation by Progesterone and Vitamin D
Yousuf S, Atif F, Espinosa-Garcia C, Harris W, Turan N, Stein D. Stroke-Induced Peripheral Immune Dysfunction in Vitamin D–Deficient Conditions: Modulation by Progesterone and Vitamin D. Molecular Neurobiology 2020, 58: 950-963. PMID: 33063282, DOI: 10.1007/s12035-020-02129-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisAstrocytesBehavior, AnimalBiomarkersCyclooxygenase 2Endoplasmic Reticulum StressHand StrengthInflammationInflammation MediatorsInterleukin-6LipopolysaccharidesMaleMyelin Basic ProteinNeuronsNitric Oxide Synthase Type IIProgesteroneRatsRats, Sprague-DawleyReactive Oxygen SpeciesReproducibility of ResultsSpleenStrokeThymus GlandTranscription Factor CHOPVitamin DVitamin D DeficiencyWhite MatterConceptsPeripheral immune dysfunctionSystemic inflammationImmune dysfunctionCombined treatmentLipopolysaccharide (LPS)-induced systemic inflammationVitamin D. Vitamin D deficiencyImmune cell populationsAdministration of progesteroneVitamin D-deficient conditionDelayed functional recoveryD sufficiencyD deficiencyEndoplasmic reticulum stressTreated with PVitamin DWhite matter integrityComorbid conditionsDay 4Improve outcomesFunctional recoveryAltered outcomesInflammationNeuronal inflammationCell populationsReticulum stress
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