2024
Disordered but effective: short linear motifs as gene therapy targets for hyperexcitability disorders
Dib-Hajj S, Waxman S. Disordered but effective: short linear motifs as gene therapy targets for hyperexcitability disorders. Journal Of Clinical Investigation 2024, 134: e182198. PMID: 38949022, PMCID: PMC11213459, DOI: 10.1172/jci182198.Peer-Reviewed Original ResearchConceptsTetrodotoxin-sensitiveHyperexcitability disordersSensory neuronsExcitability of sensory neuronsGene therapy modalitiesPeripheral sensory neuronsVoltage-gated sodiumMinimal side effectsGene therapyInduce analgesiaTherapy modalitiesSide effectsTherapeutic strategiesNav channelsAttenuating excitationIn vivoHyperexcitabilityAnalgesiaNeuronsDisordersPainTherapyGenesBiodistributionRats
2023
Conditional Astrocyte Rac1KO Attenuates Hyperreflexia after Spinal Cord Injury
Benson C, Olson K, Patwa S, Kauer S, King J, Waxman S, Tan A. Conditional Astrocyte Rac1KO Attenuates Hyperreflexia after Spinal Cord Injury. Journal Of Neuroscience 2023, 44: e1670222023. PMID: 37963762, PMCID: PMC10851682, DOI: 10.1523/jneurosci.1670-22.2023.Peer-Reviewed Original ResearchConceptsSpinal cord injuryRate-dependent depressionΑ-motor neuronsGlutamate transporter 1Dendritic spine dysgenesisCord injurySpine dysgenesisDevelopment of SCIMild contusion spinal cord injuryAstrocytic glutamate transporter 1Glial-specific glutamate transporterContusion spinal cord injuryTransporter 1Development of hyperreflexiaMonosynaptic H-reflexDendritic spine densityPre-injury levelSpinal reflex circuitsVentral spinal cordReflex hyperexcitabilityHyperexcitability disordersFunctional recoveryGlutamate clearanceH-reflexVentral hornIncreased astrocytic GLT-1 expression in tripartite synapses is associated with SCI-induced hyperreflexia
Benson C, King J, Kauer S, Waxman S, Tan A. Increased astrocytic GLT-1 expression in tripartite synapses is associated with SCI-induced hyperreflexia. Journal Of Neurophysiology 2023, 130: 1358-1366. PMID: 37877184, PMCID: PMC10972632, DOI: 10.1152/jn.00234.2023.Peer-Reviewed Original ResearchConceptsSpinal cord injuryRate-dependent depressionTripartite synapsesGLT-1Astrocytic GLT-1 expressionChronic neurological complicationsGLT-1 expressionAstrocyte involvementChronic spasticityUninjured shamsNeurological complicationsNeuropathic painHyperexcitability disordersH-reflexPSD-95 proteinReactive astrocytesVentral hornCord injuryMuscle toneAstrocytes' roleSpinal cordSpinal circuitsSynaptic transmissionHyperreflexiaSpasticity