Defective Excitatory/Inhibitory Synaptic Balance and Increased Neuron Apoptosis in a Zebrafish Model of Dravet Syndrome
Dravet syndrome is a type of severe childhood epilepsy that responds poorly to current anti-epileptic drugs. In recent years, zebrafish disease models with Scn1Lab sodium channel deficiency have been generated to seek novel anti-epileptic drug candidates, some of which are currently undergoing clini...
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MDPI AG
2019-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/10/1199 |
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| author | Alexandre Brenet Rahma Hassan-Abdi Julie Somkhit Constantin Yanicostas Nadia Soussi-Yanicostas |
| author_facet | Alexandre Brenet Rahma Hassan-Abdi Julie Somkhit Constantin Yanicostas Nadia Soussi-Yanicostas |
| author_sort | Alexandre Brenet |
| collection | DOAJ |
| description | Dravet syndrome is a type of severe childhood epilepsy that responds poorly to current anti-epileptic drugs. In recent years, zebrafish disease models with Scn1Lab sodium channel deficiency have been generated to seek novel anti-epileptic drug candidates, some of which are currently undergoing clinical trials. However, the spectrum of neuronal deficits observed following Scn1Lab depletion in zebrafish larvae has not yet been fully explored. To fill this gap and gain a better understanding of the mechanisms underlying neuron hyperexcitation in Scn1Lab-depleted larvae, we analyzed neuron activity in vivo using combined local field potential recording and transient calcium uptake imaging, studied the distribution of excitatory and inhibitory synapses and neurons as well as investigated neuron apoptosis. We found that Scn1Lab-depleted larvae displayed recurrent epileptiform seizure events, associating massive synchronous calcium uptakes and ictal-like local field potential bursts. Scn1Lab-depletion also caused a dramatic shift in the neuronal and synaptic balance toward excitation and increased neuronal death. Our results thus provide in vivo evidence suggesting that Scn1Lab loss of function causes neuron hyperexcitation as the result of disturbed synaptic balance and increased neuronal apoptosis. |
| first_indexed | 2024-03-12T07:09:40Z |
| format | Article |
| id | doaj.art-ec1dc07f88fa4057a8b320263c5d05b6 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:09:40Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ec1dc07f88fa4057a8b320263c5d05b62023-09-02T23:13:57ZengMDPI AGCells2073-44092019-10-01810119910.3390/cells8101199cells8101199Defective Excitatory/Inhibitory Synaptic Balance and Increased Neuron Apoptosis in a Zebrafish Model of Dravet SyndromeAlexandre Brenet0Rahma Hassan-Abdi1Julie Somkhit2Constantin Yanicostas3Nadia Soussi-Yanicostas4Université de Paris, NeuroDiderot, Inserm, F-75019 Paris, FranceUniversité de Paris, NeuroDiderot, Inserm, F-75019 Paris, FranceUniversité de Paris, NeuroDiderot, Inserm, F-75019 Paris, FranceUniversité de Paris, NeuroDiderot, Inserm, F-75019 Paris, FranceUniversité de Paris, NeuroDiderot, Inserm, F-75019 Paris, FranceDravet syndrome is a type of severe childhood epilepsy that responds poorly to current anti-epileptic drugs. In recent years, zebrafish disease models with Scn1Lab sodium channel deficiency have been generated to seek novel anti-epileptic drug candidates, some of which are currently undergoing clinical trials. However, the spectrum of neuronal deficits observed following Scn1Lab depletion in zebrafish larvae has not yet been fully explored. To fill this gap and gain a better understanding of the mechanisms underlying neuron hyperexcitation in Scn1Lab-depleted larvae, we analyzed neuron activity in vivo using combined local field potential recording and transient calcium uptake imaging, studied the distribution of excitatory and inhibitory synapses and neurons as well as investigated neuron apoptosis. We found that Scn1Lab-depleted larvae displayed recurrent epileptiform seizure events, associating massive synchronous calcium uptakes and ictal-like local field potential bursts. Scn1Lab-depletion also caused a dramatic shift in the neuronal and synaptic balance toward excitation and increased neuronal death. Our results thus provide in vivo evidence suggesting that Scn1Lab loss of function causes neuron hyperexcitation as the result of disturbed synaptic balance and increased neuronal apoptosis.https://www.mdpi.com/2073-4409/8/10/1199dravet syndromecalcium imaginglocal field potentialexcitatory/inhibitory balanceapoptosisin vivo imagingzebrafish<i>scn1lab</i>morpholino scn1lab<sup>aug</sup> |
| spellingShingle | Alexandre Brenet Rahma Hassan-Abdi Julie Somkhit Constantin Yanicostas Nadia Soussi-Yanicostas Defective Excitatory/Inhibitory Synaptic Balance and Increased Neuron Apoptosis in a Zebrafish Model of Dravet Syndrome Cells dravet syndrome calcium imaging local field potential excitatory/inhibitory balance apoptosis in vivo imaging zebrafish <i>scn1lab</i> morpholino scn1lab<sup>aug</sup> |
| title | Defective Excitatory/Inhibitory Synaptic Balance and Increased Neuron Apoptosis in a Zebrafish Model of Dravet Syndrome |
| title_full | Defective Excitatory/Inhibitory Synaptic Balance and Increased Neuron Apoptosis in a Zebrafish Model of Dravet Syndrome |
| title_fullStr | Defective Excitatory/Inhibitory Synaptic Balance and Increased Neuron Apoptosis in a Zebrafish Model of Dravet Syndrome |
| title_full_unstemmed | Defective Excitatory/Inhibitory Synaptic Balance and Increased Neuron Apoptosis in a Zebrafish Model of Dravet Syndrome |
| title_short | Defective Excitatory/Inhibitory Synaptic Balance and Increased Neuron Apoptosis in a Zebrafish Model of Dravet Syndrome |
| title_sort | defective excitatory inhibitory synaptic balance and increased neuron apoptosis in a zebrafish model of dravet syndrome |
| topic | dravet syndrome calcium imaging local field potential excitatory/inhibitory balance apoptosis in vivo imaging zebrafish <i>scn1lab</i> morpholino scn1lab<sup>aug</sup> |
| url | https://www.mdpi.com/2073-4409/8/10/1199 |
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