PUBLICATION

Microglia Mitigate Neuronal Activation in a Zebrafish Model of Dravet Syndrome

Authors
Brenet, A., Somkhit, J., Csaba, Z., Ciura, S., Kabashi, E., Yanicostas, C., Soussi-Yanicostas, N.
ID
ZDB-PUB-240427-4
Date
2024
Source
Cells   13(8): (Journal)
Registered Authors
Soussi-Yanicostas, Nadia
Keywords
calcium imaging, cytokines, epilepsy, microglia, neuroprotection, seizure, seizures, zebrafish
MeSH Terms
  • NAV1.1 Voltage-Gated Sodium Channel/genetics
  • NAV1.1 Voltage-Gated Sodium Channel/metabolism
  • Larva
  • Interleukin-1beta/metabolism
  • Calcium/metabolism
  • Zebrafish*
  • Microglia*/metabolism
  • Microglia*/pathology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Animals
  • Disease Models, Animal*
  • Epilepsies, Myoclonic*/genetics
  • Epilepsies, Myoclonic*/metabolism
  • Epilepsies, Myoclonic*/pathology
  • Epilepsies, Myoclonic*/physiopathology
  • Neurons*/metabolism
  • Neurons*/pathology
(all 18)
PubMed
38667299 Full text @ Cells
Abstract
It has been known for a long time that epileptic seizures provoke brain neuroinflammation involving the activation of microglial cells. However, the role of these cells in this disease context and the consequences of their inflammatory activation on subsequent neuron network activity remain poorly understood so far. To fill this gap of knowledge and gain a better understanding of the role of microglia in the pathophysiology of epilepsy, we used an established zebrafish Dravet syndrome epilepsy model based on Scn1Lab sodium channel loss-of-function, combined with live microglia and neuronal Ca2+ imaging, local field potential (LFP) recording, and genetic microglia ablation. Data showed that microglial cells in scn1Lab-deficient larvae experiencing epileptiform seizures displayed morphological and biochemical changes characteristic of M1-like pro-inflammatory activation; i.e., reduced branching, amoeboid-like morphology, and marked increase in the number of microglia expressing pro-inflammatory cytokine Il1β. More importantly, LFP recording, Ca2+ imaging, and swimming behavior analysis showed that microglia-depleted scn1Lab-KD larvae displayed an increase in epileptiform seizure-like neuron activation when compared to that seen in scn1Lab-KD individuals with microglia. These findings strongly suggest that despite microglia activation and the synthesis of pro-inflammatory cytokines, these cells provide neuroprotective activities to epileptic neuronal networks, making these cells a promising therapeutic target in epilepsy.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gl23TgTransgenic Insertion
    s552
      		Point Mutation
      zf498TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        No data available
        Fish
        No data available
        Antibodies
        No data available
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        GCaMPEFGGCaMP
        mCherryEFGmCherry
        1 - 2 of 2
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        Mapping
        No data available
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        Citation
        Brenet, A., Somkhit, J., Csaba, Z., Ciura, S., Kabashi, E., Yanicostas, C., Soussi-Yanicostas, N. (2024) Microglia Mitigate Neuronal Activation in a Zebrafish Model of Dravet Syndrome. Cells. 13(8):.