Human iPSC-derived microglia sense and dampen hyperexcitability of cortical neurons carrying the epilepsy-associated SCN2A-L1342P mutation.
Que Z, Olivero-Acosta M, Robinson M, Chen I, Zhang J, Wettschurack K, Wu J, Xiao T, Otterbacher C, Shankar V, Harlow H, Hong S, Zirkle B, Wang M, Cui N, Mandal P, Chen X, Deming B, Halurkar M, Zhao Y, Rochet J, Xu R, Brewster A, Wu L, Yuan C, Skarnes W, Yang Y. Human iPSC-derived microglia sense and dampen hyperexcitability of cortical neurons carrying the epilepsy-associated SCN2A-L1342P mutation. Journal Of Neuroscience 2024, e2027232024. PMID: 39557580, DOI: 10.1523/jneurosci.2027-23.2024.Peer-Reviewed Original ResearchNeuronal excitabilityHyperexcitable neuronsHuman microgliaCo-cultureVoltage-gated sodium channel Nav1.2Neuronal activityRepetitive action potential firingRodent models of seizuresBrain-resident immune cellsSodium channel expressionInfluence neuronal excitabilityAction potential firingHyperexcitability of cortical neuronsModulates neuronal excitabilityEpilepsy-causing mutationsSodium channel Nav1.2Resident immune cellsAbnormal neuronal activityPresence of microgliaSuppression of seizuresModulate neuronal activityDensity of sodium channelsModels of seizuresPresence of neuronsAxon initial segment