Early maturation and hyperexcitability is a shared phenotype of cortical neurons derived from different ASD-associated mutations.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
06 Jul 2023
06 Jul 2023
Historique:
received:
11
05
2023
accepted:
21
06
2023
revised:
18
06
2023
medline:
10
7
2023
pubmed:
7
7
2023
entrez:
6
7
2023
Statut:
epublish
Résumé
Autism Spectrum Disorder (ASD) is characterized mainly by social and sensory-motor abnormal and repetitive behavior patterns. Over hundreds of genes and thousands of genetic variants were reported to be highly penetrant and causative of ASD. Many of these mutations cause comorbidities such as epilepsy and intellectual disabilities (ID). In this study, we measured cortical neurons derived from induced pluripotent stem cells (iPSCs) of patients with four mutations in the genes GRIN2B, SHANK3, UBTF, as well as chromosomal duplication in the 7q11.23 region and compared them to neurons derived from a first-degree relative without the mutation. Using a whole-cell patch-clamp, we observed that the mutant cortical neurons demonstrated hyperexcitability and early maturation compared to control lines. These changes were characterized by increased sodium currents, increased amplitude and rate of excitatory postsynaptic currents (EPSCs), and more evoked action potentials in response to current stimulation in early-stage cell development (3-5 weeks post differentiation). These changes that appeared in all the different mutant lines, together with previously reported data, indicate that an early maturation and hyperexcitability may be a convergent phenotype of ASD cortical neurons.
Identifiants
pubmed: 37414777
doi: 10.1038/s41398-023-02535-x
pii: 10.1038/s41398-023-02535-x
pmc: PMC10326262
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
246Subventions
Organisme : Israel Science Foundation (ISF)
ID : 352/21
Informations de copyright
© 2023. The Author(s).
Références
Nat Neurosci. 2019 Feb;22(2):243-255
pubmed: 30617258
Cell Tissue Res. 2006 Nov;326(2):409-22
pubmed: 16865346
Dialogues Clin Neurosci. 2012 Sep;14(3):281-92
pubmed: 23226953
Neuron. 1999 Jul;23(3):569-82
pubmed: 10433268
Transl Psychiatry. 2020 Jul 13;10(1):228
pubmed: 32661233
Nat Commun. 2020 Oct 12;11(1):5140
pubmed: 33046712
Science. 2006 Oct 6;314(5796):122-5
pubmed: 17023658
BMC Neurosci. 2021 Sep 15;22(1):56
pubmed: 34525970
Brain Res. 2022 Oct 15;1793:148053
pubmed: 35973608
Nature. 2012 Apr 04;485(7397):242-5
pubmed: 22495311
J Med Genet. 2017 Jul;54(7):460-470
pubmed: 28377535
Mol Psychiatry. 2018 Jun;23(6):1453-1465
pubmed: 28242870
Annu Rev Cell Dev Biol. 2008;24:131-57
pubmed: 18616426
Stem Cell Reports. 2018 Jul 10;11(1):183-196
pubmed: 29937144
Am J Med Genet A. 2013 Oct;161A(10):2564-9
pubmed: 23918416
J Cell Sci. 2000 Jun;113 ( Pt 11):1851-6
pubmed: 10806096
Mol Autism. 2019 Dec 30;10:52
pubmed: 31893021
Development. 2003 Jan;130(2):411-23
pubmed: 12466207
Neuron. 2011 Jun 9;70(5):863-85
pubmed: 21658581
Neural Regen Res. 2013 Oct 15;8(29):2734-43
pubmed: 25206584
J Pharmacol Sci. 2016 Oct;132(2):115-121
pubmed: 27818011
Epilepsia. 2016 Oct;57(10):1651-1659
pubmed: 27554343
Behav Brain Funct. 2013 May 29;9:20
pubmed: 23718928
Hum Genet. 2010 Jul;128(1):3-26
pubmed: 20437059
Nat Genet. 1993 Sep;5(1):11-6
pubmed: 7693128
Transl Psychiatry. 2021 Sep 17;11(1):480
pubmed: 34535637
Acta Paedopsychiatr. 1968;35(4):100-36
pubmed: 4880460
Neuron. 2014 Mar 19;81(6):1282-1289
pubmed: 24656250
Mol Psychiatry. 2022 Aug;27(8):3316-3327
pubmed: 35538192
Nat Rev Neurosci. 2017 Mar;18(3):147-157
pubmed: 28179641
NPJ Parkinsons Dis. 2022 Aug 10;8(1):103
pubmed: 35948563
Ann Neurol. 2014 Jan;75(1):147-54
pubmed: 24272827
Int J Mol Sci. 2022 Feb 12;23(4):
pubmed: 35216162
Nature. 2011 Apr 28;472(7344):437-42
pubmed: 21423165
Biol Psychiatry. 2017 May 15;81(10):838-847
pubmed: 27450033
Int J Biochem Cell Biol. 1999 Feb;31(2):261-72
pubmed: 10216959
Brain. 2020 Apr 1;143(4):1099-1105
pubmed: 32168371
Nature. 1997 Mar 20;386(6622):221, 223
pubmed: 9069275
Elife. 2021 Jul 02;10:
pubmed: 34212862
Nat Rev Neurosci. 2009 May;10(5):319-32
pubmed: 19377501
J Neurosci. 2021 Dec 8;41(49):10194-10208
pubmed: 34716231
Epilepsy Curr. 2007 Jan-Feb;7(1):15-22
pubmed: 17304346
Acta Neuropathol. 2017 Oct;134(4):537-566
pubmed: 28584888
Lancet. 2018 Aug 11;392(10146):508-520
pubmed: 30078460
Pharmacol Rev. 2010 Sep;62(3):405-96
pubmed: 20716669
Cell Stem Cell. 2018 May 3;22(5):684-697.e9
pubmed: 29727680
Neuron. 1994 Mar;12(3):529-40
pubmed: 7512349
Hum Mol Genet. 1999;8(10):1947-54
pubmed: 10469848
Schizophr Res. 2022 Nov 25;:
pubmed: 36443183
J Neurosci. 2019 Sep 11;39(37):7438-7449
pubmed: 31350261
Curr Opin Neurobiol. 2001 Jun;11(3):327-35
pubmed: 11399431
Biol Psychiatry. 2020 Jul 15;88(2):150-158
pubmed: 32278494
Neuropediatrics. 2019 Feb;50(1):57-60
pubmed: 30517966
Mol Psychiatry. 2001 Mar;6(2):211-6
pubmed: 11317224
Hum Mol Genet. 2018 Feb 15;27(4):691-705
pubmed: 29300972
Cold Spring Harb Perspect Biol. 2012 Mar 01;4(3):
pubmed: 22258914
Nature. 2013 Jan 17;493(7432):371-7
pubmed: 23172145
Front Neurosci. 2021 Oct 28;15:751364
pubmed: 34776852
Brain Sci. 2017 Oct 13;7(10):
pubmed: 29027913
Sci Rep. 2018 Jul 24;8(1):11138
pubmed: 30042445
Nature. 2012 Sep 20;489(7416):385-90
pubmed: 22914087
Stem Cell Res. 2022 Oct;64:102899
pubmed: 36044808
Mol Psychiatry. 2021 May;26(5):1619-1633
pubmed: 31664177
Autism Res. 2021 Aug;14(8):1684-1694
pubmed: 34042279
Mol Autism. 2010 Dec 17;1(1):15
pubmed: 21167025
Biol Psychiatry. 2021 Dec 1;90(11):756-765
pubmed: 34538422
Nat Rev Neurosci. 2015 Sep;16(9):551-63
pubmed: 26289574
Front Cell Neurosci. 2018 Aug 03;12:234
pubmed: 30123111
Neuron. 1996 Feb;16(2):333-44
pubmed: 8789948
Am J Med Genet A. 2015 Dec;167A(12):2916-35
pubmed: 26333794
J Neurosci. 2009 Sep 2;29(35):10869-82
pubmed: 19726645
J Med Genet. 2006 Oct;43(10):822-8
pubmed: 16284256
Mol Autism. 2016 Oct 21;7:44
pubmed: 27790361
Mol Psychiatry. 2021 Nov;26(11):6550-6561
pubmed: 33967268
Nature. 2011 May 12;473(7346):221-5
pubmed: 21490598
Nat Genet. 2007 Jan;39(1):25-7
pubmed: 17173049
J Med Genet. 2003 Aug;40(8):575-84
pubmed: 12920066
Int J Mol Sci. 2023 Apr 18;24(8):
pubmed: 37108598
Oncotarget. 2015 Sep 29;6(29):27519-36
pubmed: 26317157
Am J Hum Genet. 2019 May 2;104(5):815-834
pubmed: 31031012
Mol Psychiatry. 2021 Dec;26(12):7498-7508
pubmed: 34535765
J Neural Transm (Vienna). 2014 Aug;121(8):891-905
pubmed: 24752754
Neurosci Biobehav Rev. 2012 Oct;36(9):2044-55
pubmed: 22841562
Neurol Sci. 2021 Mar;42(3):1217-1219
pubmed: 33026538
Mol Psychiatry. 2020 Aug;25(8):1835-1848
pubmed: 29988084
Mol Autism. 2013 Jun 11;4(1):18
pubmed: 23758760
Am J Hum Genet. 2017 Aug 3;101(2):267-273
pubmed: 28777933
Genomics. 1994 Jul 1;22(1):216-8
pubmed: 7959773
Am J Med Genet A. 2015 Jul;167(7):1436-50
pubmed: 25900101
BMC Neurol. 2020 Jan 13;20(1):17
pubmed: 31931739
Genes Brain Behav. 2003 Oct;2(5):255-67
pubmed: 14606691