Spine impairment in mice high-expressing neuregulin 1 due to LIMK1 activation.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
14 04 2021
14 04 2021
Historique:
received:
18
11
2020
accepted:
30
03
2021
revised:
30
03
2021
entrez:
15
4
2021
pubmed:
16
4
2021
medline:
18
9
2021
Statut:
epublish
Résumé
The genes encoding for neuregulin1 (NRG1), a growth factor, and its receptor ErbB4 are both risk factors of major depression disorder and schizophrenia (SZ). They have been implicated in neural development and synaptic plasticity. However, exactly how NRG1 variations lead to SZ remains unclear. Indeed, NRG1 levels are increased in postmortem brain tissues of patients with brain disorders. Here, we studied the effects of high-level NRG1 on dendritic spine development and function. We showed that spine density in the prefrontal cortex and hippocampus was reduced in mice (ctoNrg1) that overexpressed NRG1 in neurons. The frequency of miniature excitatory postsynaptic currents (mEPSCs) was reduced in both brain regions of ctoNrg1 mice. High expression of NRG1 activated LIMK1 and increased cofilin phosphorylation in postsynaptic densities. Spine reduction was attenuated by inhibiting LIMK1 or blocking the NRG1-LIMK1 interaction, or by restoring NRG1 protein level. These results indicate that a normal NRG1 protein level is necessary for spine homeostasis and suggest a pathophysiological mechanism of abnormal spines in relevant brain disorders.
Identifiants
pubmed: 33854034
doi: 10.1038/s41419-021-03687-8
pii: 10.1038/s41419-021-03687-8
pmc: PMC8047019
doi:
Substances chimiques
Neuregulin-1
0
Nrg1 protein, mouse
0
Receptor, ErbB-4
EC 2.7.10.1
Lim Kinases
EC 2.7.11.1
Limk1 protein, mouse
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
403Références
Trends Cell Biol. 2010 Apr;20(4):187-95
pubmed: 20133134
Nat Neurosci. 2019 Mar;22(3):353-361
pubmed: 30692689
Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9387-91
pubmed: 7937775
Nature. 2006 Jan 19;439(7074):283-9
pubmed: 16421561
Neuron. 2017 Apr 19;94(2):304-311.e4
pubmed: 28426965
Neuropsychopharmacology. 2012 Aug;37(9):2088-92
pubmed: 22549119
Am J Psychiatry. 2016 Jan;173(1):60-8
pubmed: 26337038
Neuron. 2000 May;26(2):443-55
pubmed: 10839362
Neuron. 2014 Jul 2;83(1):27-49
pubmed: 24991953
Dis Model Mech. 2012 Jan;5(1):26-32
pubmed: 21954066
Neuroreport. 2020 Jun 7;31(9):678-685
pubmed: 32427713
Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4507-12
pubmed: 19240213
Nature. 2010 Apr 29;464(7293):1376-80
pubmed: 20393464
Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6747-52
pubmed: 16618933
Schizophr Res. 2011 Sep;131(1-3):52-7
pubmed: 21745728
J Neurosci. 2005 Mar 30;25(13):3379-88
pubmed: 15800193
Nature. 1998 Jan 1;391(6662):93-6
pubmed: 9422512
Mol Psychiatry. 2005 Apr;10(4):366-74, 328
pubmed: 15545978
J Neurosci. 2011 Jan 5;31(1):15-25
pubmed: 21209185
Neuron. 2002 Jul 3;35(1):3-5
pubmed: 12123600
Schizophr Res. 2008 Mar;100(1-3):270-80
pubmed: 18243664
Nat Med. 2006 Jul;12(7):824-8
pubmed: 16767099
J Biol Chem. 2001 Jan 26;276(4):2841-51
pubmed: 11042203
J Neurosci. 2008 Jul 2;28(27):6872-83
pubmed: 18596162
Neuron. 2004 Oct 14;44(2):251-61
pubmed: 15473965
Am J Psychiatry. 2005 Jun;162(6):1200-2
pubmed: 15930070
Arch Gen Psychiatry. 2000 Jan;57(1):65-73
pubmed: 10632234
J Neurosci. 2011 Aug 10;31(32):11628-32
pubmed: 21832192
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3739-44
pubmed: 10097107
Science. 2008 Apr 25;320(5875):539-43
pubmed: 18369103
Nature. 2014 Jul 24;511(7510):421-7
pubmed: 25056061
Neuron. 1995 Jan;14(1):103-15
pubmed: 7530017
Neuron. 2013 Sep 18;79(6):1152-68
pubmed: 24050403
Neuron. 2017 Jun 21;94(6):1155-1172.e8
pubmed: 28641114
Transl Psychiatry. 2017 Jan 17;7(1):e1004
pubmed: 28094814
Neuron. 2002 Jul 3;35(1):121-33
pubmed: 12123613
J Neurosci. 2016 Apr 27;36(17):4859-75
pubmed: 27122041
Nature. 1998 Jun 25;393(6687):809-12
pubmed: 9655398
Exp Neurol. 2011 Dec;232(2):222-33
pubmed: 21963650
Synapse. 2005 Jul;57(1):47-55
pubmed: 15858835
Mol Psychiatry. 2004 Mar;9(3):299-307
pubmed: 14569272
Physiol Behav. 2016 Feb 1;154:145-50
pubmed: 26626816
World J Biol Psychiatry. 2010 Mar;11(2 Pt 2):243-50
pubmed: 20218788
Brain Res. 2000 Feb 28;857(1-2):265-74
pubmed: 10700575
Transl Psychiatry. 2017 Jul 4;7(7):e1161
pubmed: 28675388
Brain Res Bull. 2010 Sep 30;83(3-4):122-31
pubmed: 20688137
Nat Neurosci. 2002 Mar;5(3):239-46
pubmed: 11850630
Proc Natl Acad Sci U S A. 2018 Mar 6;115(10):2508-2513
pubmed: 29463705
J Neurosci. 2014 Oct 1;34(40):13549-66
pubmed: 25274830
Mol Biol Cell. 2014 Mar;25(6):828-40
pubmed: 24478456
J Neurol Neurosurg Psychiatry. 1998 Oct;65(4):446-53
pubmed: 9771764
PLoS One. 2010 Dec 09;5(12):e14185
pubmed: 21151609
J Biol Chem. 1998 Aug 7;273(32):20525-34
pubmed: 9685409
Mol Psychiatry. 2003 Jul;8(7):706-9
pubmed: 12874607
Proc Natl Acad Sci U S A. 1982 Dec;79(23):7590-4
pubmed: 6760199
Neurosci Lett. 2015 Oct 8;606:220-4
pubmed: 26365407
Nat Neurosci. 2019 Mar;22(3):343-352
pubmed: 30718901
Cereb Cortex. 2012 Jul;22(7):1520-9
pubmed: 21878485
Arch Gen Psychiatry. 2010 Oct;67(10):991-1001
pubmed: 20921115
Cereb Cortex. 2000 Oct;10(10):927-38
pubmed: 11007543
Nat Neurosci. 2012 Nov;15(11):1506-15
pubmed: 23064382
Nature. 2009 Aug 6;460(7256):753-7
pubmed: 19571809
Transl Psychiatry. 2020 Jul 23;10(1):249
pubmed: 32703967
Nat Med. 2012 Sep;18(9):1413-7
pubmed: 22885997
Nat Neurosci. 2004 Apr;7(4):364-72
pubmed: 15034583
Hum Mol Genet. 2006 Jun 15;15(12):1995-2002
pubmed: 16687441
Science. 1996 Dec 6;274(5293):1678-83
pubmed: 8939850
Curr Biol. 2013 Sep 9;23(17):R764-73
pubmed: 24028960
J Neurosci. 2013 Dec 4;33(49):19295-303
pubmed: 24305825
Neurosci Lett. 2015 Aug 5;601:46-53
pubmed: 25478958
J Biol Chem. 1995 Mar 3;270(9):4784-91
pubmed: 7876251
Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9985-9
pubmed: 7937931
Neuron. 2000 Oct;28(1):41-51
pubmed: 11086982
Neuron. 2013 May 22;78(4):644-57
pubmed: 23719163
Neuroreport. 2009 Nov 25;20(17):1523-8
pubmed: 19829162
J Psychiatr Res. 2010 Dec;44(16):1205-13
pubmed: 20471034
Am J Hum Genet. 2002 Oct;71(4):877-92
pubmed: 12145742
Int J Neuropsychopharmacol. 2020 Dec 29;23(12):821-836
pubmed: 32827213