Scn1a gene reactivation after symptom onset rescues pathological phenotypes in a mouse model of Dravet syndrome.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
10 01 2022
Historique:
received: 17 04 2021
accepted: 14 12 2021
entrez: 11 1 2022
pubmed: 12 1 2022
medline: 11 2 2022
Statut: epublish

Résumé

Dravet syndrome is a severe epileptic encephalopathy caused primarily by haploinsufficiency of the SCN1A gene. Repetitive seizures can lead to endurable and untreatable neurological deficits. Whether this severe pathology is reversible after symptom onset remains unknown. To address this question, we generated a Scn1a conditional knock-in mouse model (Scn1a 

Identifiants

pubmed: 35013317
doi: 10.1038/s41467-021-27837-w
pii: 10.1038/s41467-021-27837-w
pmc: PMC8748984
doi:

Substances chimiques

NAV1.1 Voltage-Gated Sodium Channel 0
Scn1a protein, mouse 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

161

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2022. The Author(s).

Références

Brunklaus, A., Ellis, R., Reavey, E., Semsarian, C. & Zuberi, S. M. Genotype phenotype associations across the voltage-gated sodium channel family. J. Med. Genet. 51, 650–658 (2014).
pubmed: 25163687 doi: 10.1136/jmedgenet-2014-102608
Catterall, W. A. Dravet syndrome: A sodium channel interneuronopathy. Curr. Opin. Physiol. 2, 42–50 (2018).
pubmed: 30123852 doi: 10.1016/j.cophys.2017.12.007
Hudry, E. & Vandenberghe, L. H. Therapeutic AAV gene transfer to the nervous system: A clinical reality. Neuron. 101, 839–862 (2019).
pubmed: 30844402 doi: 10.1016/j.neuron.2019.02.017
Deverman, B. E., Ravina, B. M., Bankiewicz, K. S., Paul, S. M. & Sah, D. W. Y. Gene therapy for neurological disorders: Progress and prospects. Nat. Rev. Drug Discov. 17, 641–659 (2018).
pubmed: 30093643 doi: 10.1038/nrd.2018.110
Hsiao, J. et al. Upregulation of haploinsufficient gene expression in the brain by targeting a long non-coding RNA improves seizure phenotype in a model of dravet syndrome. EBioMedicine. 9, 257–277 (2016).
pubmed: 27333023 pmcid: 4972487 doi: 10.1016/j.ebiom.2016.05.011
Colasante, G. et al. dCas9-Based Scn1a gene activation restores inhibitory interneuron excitability and attenuates seizures in Dravet syndrome mice. Mol Ther. https://doi.org/10.1016/j.ymthe.2019.08.018 (2019).
Yamagata, T. et al. CRISPR/dCas9-based Scn1a gene activation in inhibitory neurons ameliorates epileptic and behavioral phenotypes of Dravet syndrome model mice. Neurobiol. Dis. 141. https://doi.org/10.1016/j.nbd.2020.104954 (2020).
Lim, K. H. et al. Antisense oligonucleotide modulation of non-productive alternative splicing upregulates gene expression. Nat. Commun. 11. https://doi.org/10.1038/s41467-020-17093-9 (2020).
Han, Z. et al. Antisense oligonucleotides increase Scn1a expression and reduce seizures and SUDEP incidence in a mouse model of Dravet syndrome. Sci. Transl. Med. 12. https://doi.org/10.1126/SCITRANSLMED.AAZ6100 (2020).
Favero, M., Sotuyo, N. P., Lopez, E., Kearney, J. A. & Goldberg, E. M. A transient developmental window of fast-spiking interneuron dysfunction in a mouse model of Dravet Syndrome. J. Neurosci. 38, 7912–7927 (2018).
pubmed: 30104343 pmcid: 6125809 doi: 10.1523/JNEUROSCI.0193-18.2018
Ricobaraza, A. et al. Epilepsy and neuropsychiatric comorbidities in mice carrying a recurrent Dravet syndrome SCN1A missense mutation. Sci. Rep. 9, 14172 (2019).
pubmed: 31578435 pmcid: 6775062 doi: 10.1038/s41598-019-50627-w
Kalume, F., Catterall, W. A., Westenbroek, R. E., Yu, F. H. & Scheuer, T. Reduced sodium current in Purkinje neurons from NaV1.1 mutant mice: Implications for Ataxia in severe myoclonic epilepsy in infancy. J. Neurosci. 27, 11065–11074 (2007).
pubmed: 17928448 pmcid: 6672849 doi: 10.1523/JNEUROSCI.2162-07.2007
Yu, F. H. et al. Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy. Nat. Neurosci. 9, 1142–1149 (2006).
pubmed: 16921370 doi: 10.1038/nn1754
Ogiwara, I. et al. Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: A circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. J. Neurosci. 27, 5903–5914 (2007).
pubmed: 17537961 pmcid: 6672241 doi: 10.1523/JNEUROSCI.5270-06.2007
Chan, K. Y. et al. Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems. Nat. Neurosci. 20, 1172–1179 (2017).
pubmed: 28671695 pmcid: 5529245 doi: 10.1038/nn.4593
Han, S. et al. Autistic-like behaviour in Scn1a +/− mice and rescue by enhanced GABA-mediated neurotransmission. Nature. 489, 385–390 (2012).
pubmed: 22914087 pmcid: 3448848 doi: 10.1038/nature11356
Ito, S. et al. Mouse with Nav1.1 haploinsufficiency, a model for Dravet syndrome, exhibits lowered sociability and learning impairment. Neurobiol. Dis. 49, 29–40 (2013).
pubmed: 22986304 doi: 10.1016/j.nbd.2012.08.003
Vorhees, C. V. & Williams, M. T. Morris water maze: Procedures for assessing spatial and related forms of learning and memory. Nat. Protoc. 1, 848–858 (2006).
pubmed: 17406317 pmcid: 2895266 doi: 10.1038/nprot.2006.116
Tai, C., Abe, Y., Westenbroek, R. E., Scheuer, T. & Catterall, W. A. Impaired excitability of somatostatin- and parvalbumin-expressing cortical interneurons in a mouse model of Dravet syndrome. Proc. Natl Acad. Sci. USA. 111, E3139–E3148 (2014).
pubmed: 25024183 pmcid: 4121787
Mistry, A. M. et al. Strain- and age-dependent hippocampal neuron sodium currents correlate with epilepsy severity in Dravet syndrome mice. Neurobiol. Dis. 65, 1–11 (2014).
pubmed: 24434335 pmcid: 3968814 doi: 10.1016/j.nbd.2014.01.006
Goff, K. M. & Goldberg, E. M. Vasoactive intestinal peptide-expressing interneurons are impaired in a mouse model of dravet syndrome. Elife. 8. https://doi.org/10.7554/eLife.46846 (2019).
Tamamaki, N. et al. Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67-GFP knock-in mouse. J. Comp. Neurol. 467, 60–79 (2003).
pubmed: 14574680 doi: 10.1002/cne.10905
Arion, D. et al. Correlation of transcriptome profile with electrical activity in temporal lobe epilepsy. Neurobiol. Dis. 22, 374–387 (2006).
pubmed: 16480884 doi: 10.1016/j.nbd.2005.12.012
Dixit, A. B. et al. RNA-seq analysis of hippocampal tissues reveals novel candidate genes for drug refractory epilepsy in patients with MTLE-HS. Genomics 107, 178–188 (2016).
pubmed: 27094248 doi: 10.1016/j.ygeno.2016.04.001
Jamali, S. et al. Large-scale expression study of human mesial temporal lobe epilepsy: Evidence for dysregulation of the neurotransmission and complement systems in the entorhinal cortex. Brain 129, 625–641 (2006).
pubmed: 16399808 doi: 10.1093/brain/awl001
Mirza, N., Vasieva, O., Marson, A. G. & Pirmohamed, M. Exploring the genomic basis of pharmacoresistance in epilepsy: An integrative analysis of large-scale gene expression profiling studies on brain tissue from epilepsy surgery. Hum. Mol. Genet. 20, 4381–4394 (2011).
pubmed: 21852245 pmcid: 3196887 doi: 10.1093/hmg/ddr365
Colasante, G. et al. In vivo CRISPRa decreases seizures and rescues cognitive deficits in a rodent model of epilepsy. Brain. 143, 891–905 (2020).
pubmed: 32129831 pmcid: 7089667 doi: 10.1093/brain/awaa045
Sprissler, R. S., Wagnon, J. L., Bunton-Stasyshyn, R. K., Meisler, M. H. & Hammer, M. F. Altered gene expression profile in a mouse model of SCN8A encephalopathy. Exp. Neurol. 288, 134–141 (2017).
pubmed: 27836728 doi: 10.1016/j.expneurol.2016.11.002
Miller, A. R., Hawkins, N. A., Mccollom, C. E. & Kearney, J. A. Mapping genetic modifiers of survival in a mouse model of Dravet syndrome. Genes, Brain Behav. 13, 163–172 (2014).
doi: 10.1111/gbb.12099
Hawkins, N. A., Zachwieja, N. J., Miller, A. R., Anderson, L. L. & Kearney, J. A. Fine mapping of a Dravet syndrome modifier locus on mouse chromosome 5 and candidate gene analysis by RNA-Seq. PLoS. Genet. 12, 1–15 (2016).
doi: 10.1371/journal.pgen.1006398
Vezzani, A., French, J., Bartfai, T. & Baram, T. Z. The role of inflammation in epilepsy. Nat. Rev. Neurol. 7, 31–40 (2011).
pubmed: 21135885 doi: 10.1038/nrneurol.2010.178
Vezzani, A., Lang, B. & Aronica, E. Immunity and inflammation in epilepsy. Cold. Spring. Harb. Perspect. Med. 6. https://doi.org/10.1101/cshperspect.a022699 (2016).
Devinsky, O., Vezzani, A., Najjar, S., De Lanerolle, N. C. & Rogawski, M. A. Glia and epilepsy: Excitability and inflammation. Trends Neurosci. 36, 174–184 (2013).
pubmed: 23298414 doi: 10.1016/j.tins.2012.11.008
Martín-Suárez, S., Abiega, O., Ricobaraza, A., Hernandez-Alcoceba, R. & Encinas, J. M. Alterations of the Hippocampal Neurogenic Niche in a Mouse Model of Dravet Syndrome. Front. Cell. Dev. Biol. 8. https://doi.org/10.3389/fcell.2020.00654 (2020).
Zamanian, J. L. et al. Genomic analysis of reactive astrogliosis. J. Neurosci. 32, 6391–6410 (2012).
pubmed: 22553043 pmcid: 3480225 doi: 10.1523/JNEUROSCI.6221-11.2012
Liddelow, S. A. et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 541, 481–487 (2017).
pubmed: 28099414 pmcid: 5404890 doi: 10.1038/nature21029
Semple, B. D., Blomgren, K., Gimlin, K., Ferriero, D. M. & Noble-Haeusslein, L. J. Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species. Prog. Neurobiol. 106-107, 1–16 (2013).
pubmed: 23583307 doi: 10.1016/j.pneurobio.2013.04.001
Dutta, S. & Sengupta, P. Men and mice: Relating their ages. Life Sci. 152, 244–248 (2016).
pubmed: 26596563 doi: 10.1016/j.lfs.2015.10.025
Wirrell, E. C. Treatment of Dravet Syndrome. Can. J. Neurol. Sci. / J. Can. des. Sci. Neurol. 43, S13–S18 (2016).
doi: 10.1017/cjn.2016.249
Nickels, K. C. & Wirrell, E. C. Cognitive and social outcomes of epileptic encephalopathies. Semin Pediatr. Neurol. 24, 264–275 (2017).
pubmed: 29249506 doi: 10.1016/j.spen.2017.10.001
Nabbout, R. et al. Encephalopathy in children with Dravet syndrome is not a pure consequence of epilepsy. Orphanet. J. Rare. Dis. 8. https://doi.org/10.1186/1750-1172-8-176 (2013).
Ouss, L. et al. Autism spectrum disorder and cognitive profile in children with Dravet syndrome: Delineation of a specific phenotype. Epilepsia. Open. 4, 40–53 (2019).
pubmed: 30868114 doi: 10.1002/epi4.12281
Chieffo, D. et al. Neuropsychological development in children with Dravet syndrome. Epilepsy. Res. 95, 86–93 (2011).
pubmed: 21474289 doi: 10.1016/j.eplepsyres.2011.03.005
Guzzetta, F. Cognitive and behavioral characteristics of children with Dravet syndrome: An overview. Epilepsia. 52, 35–38 (2011). SUPPL. 2.
pubmed: 21463277 doi: 10.1111/j.1528-1167.2011.02999.x
Fadila, S. et al. Convulsive seizures and some behavioral comorbidities are uncoupled in the Scn1aA1783V Dravet syndrome mouse model. Epilepsia. 61, 2289–2300 (2020).
pubmed: 32865826 doi: 10.1111/epi.16662
Stein, R. E., Kaplan, J. S., Li, J. & Catterall, W. A. Hippocampal deletion of NaV1.1 channels in mice causes thermal seizures and cognitive deficit characteristic of Dravet Syndrome. Proc. Natl Acad. Sci. USA. 116, 16571–16576 (2019).
pubmed: 31346088 pmcid: 6697805 doi: 10.1073/pnas.1906833116
Christopherson, K. S. et al. Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis. Cell. 120, 421–433 (2005).
pubmed: 15707899 doi: 10.1016/j.cell.2004.12.020
Eroglu, Ç. et al. Gabapentin receptor α2δ-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis. Cell. 139, 380–392 (2009).
pubmed: 19818485 pmcid: 2791798 doi: 10.1016/j.cell.2009.09.025
Stevens, B. et al. The classical complement cascade mediates CNS synapse elimination. Cell. 131, 1164–1178 (2007).
pubmed: 18083105 doi: 10.1016/j.cell.2007.10.036
Lin, S., Staahl, B., Alla, R. K. & Doudna, J. A. Enhanced homology-directed human genome engineering by controlled. Elife. 3, e04766 (2014).
pubmed: 25497837 pmcid: 4383097 doi: 10.7554/eLife.04766
Catarino, C. B. et al. Dravet syndrome as epileptic encephalopathy: evidence from long-term course and neuropathology. Brain. 134, 2982–3010 (2011).
pubmed: 21719429 pmcid: 3187538 doi: 10.1093/brain/awr129
Jackson, E. L. et al. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev. 15, 3243–3248 (2001).
pubmed: 11751630 pmcid: 312845 doi: 10.1101/gad.943001
Guy, J., Gan, J., Selfridge, J., Cobb, S. & Bird, A. Reversal of neurological defects in a mouse model of Rett syndrome. Science (80-) 315, 1143–1147 (2007).
doi: 10.1126/science.1138389
Lampe, S. E. G., Kaspar, B. K. & Foust, K. D. Intravenous injections in neonatal mice. J. Vis. Exp. https://doi.org/10.3791/52037 (2014).
Oakley, J. C., Kalume, F., Yu, F. H., Scheuer, T. & Catterall, W. A. Temperature- and age-dependent seizures in a mouse model of severe myoclonic epilepsy in infancy. Proc. Natl Acad. Sci. 106, 3994–3999 (2009).
pubmed: 19234123 pmcid: 2656193 doi: 10.1073/pnas.0813330106
Wolfer, D. P. & Lipp, H. P. A new computer program for detailed off-line analysis of swimming navigation in the Morris water maze. J. Neurosci. Meth. 41, 65–74 (1992).
doi: 10.1016/0165-0270(92)90124-V
Balschun, D. et al. Does cAMP response element-binding protein have a pivotal role in hippocampal synaptic plasticity and hippocampus-dependent memory? J. Neurosci. 23, 6304–6314 (2003).
pubmed: 12867515 pmcid: 6740551 doi: 10.1523/JNEUROSCI.23-15-06304.2003
Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatic.s 30, 2114–2120 (2014).
doi: 10.1093/bioinformatics/btu170
Dobin, A. & Gingeras, T. R. Optimizing RNA-seq mapping with STAR. In Methods in Molecular Biology. 1415, 245–262. (Humana Press Inc., 2016).
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome. Biol. 15, 550 (2014).
pubmed: 25516281 pmcid: 4302049 doi: 10.1186/s13059-014-0550-8
Subhash, S., Andersson, P. O., Kosalai, S. T., Kanduri, C. & Kanduri, M. Global DNA methylation profiling reveals new insights into epigenetically deregulated protein coding and long noncoding RNAs in CLL. Clin. Epigenetics. 8. https://doi.org/10.1186/s13148-016-0274-6 (2016).

Auteurs

Nicholas Valassina (N)

Stem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.

Simone Brusco (S)

Stem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.

Alessia Salamone (A)

Stem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.

Linda Serra (L)

Stem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.

Mirko Luoni (M)

Stem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.

Serena Giannelli (S)

Stem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.

Simone Bido (S)

Stem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.

Luca Massimino (L)

Humanitas Clinical and Research Center - IRCCS, Rozzano, Milan, Italy.

Federica Ungaro (F)

Humanitas Clinical and Research Center - IRCCS, Rozzano, Milan, Italy.

Pietro Giuseppe Mazzara (PG)

Stem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.
Department of Genetics and Development, Columbia University, 10032, New York, NY, USA.

Patrizia D'Adamo (P)

Molecular Genetics of Intellectual Disability, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.
Mouse behavior Core Facility, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.

Gabriele Lignani (G)

Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.

Vania Broccoli (V)

Stem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy. broccoli.vania@hsr.it.
National Research Council (CNR), Institute of Neuroscience, 20129, Milan, Italy. broccoli.vania@hsr.it.

Gaia Colasante (G)

Stem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy. colasante.gaia@hsr.it.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH