Bipolar-associated miR-499-5p controls neuroplasticity by downregulating the Cav1.2 subunit CACNB2.
bipolar disorder
calcium channel
cognitive function
microRNA
neuroplasticity
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
06 10 2022
06 10 2022
Historique:
revised:
21
07
2022
received:
01
12
2021
accepted:
26
07
2022
pubmed:
16
8
2022
medline:
12
10
2022
entrez:
15
8
2022
Statut:
ppublish
Résumé
Bipolar disorder (BD) is a chronic mood disorder characterized by manic and depressive episodes. Dysregulation of neuroplasticity and calcium homeostasis are frequently observed in BD patients, but the underlying molecular mechanisms are largely unknown. Here, we show that miR-499-5p regulates dendritogenesis and cognitive function by downregulating the BD risk gene CACNB2. miR-499-5p expression is increased in peripheral blood of BD patients, as well as in the hippocampus of rats which underwent juvenile social isolation. In rat hippocampal neurons, miR-499-5p impairs dendritogenesis and reduces surface expression and activity of the L-type calcium channel Cav1.2. We further identified CACNB2, which encodes a regulatory β-subunit of Cav1.2, as a direct functional target of miR-499-5p in neurons. miR-499-5p overexpression in the hippocampus in vivo induces short-term memory impairments selectively in rats haploinsufficient for the Cav1.2 pore forming subunit Cacna1c. In humans, miR-499-5p expression is negatively associated with gray matter volumes of the left superior temporal gyrus, a region implicated in auditory and emotional processing. We propose that stress-induced miR-499-5p overexpression contributes to dendritic impairments, deregulated calcium homeostasis, and neurocognitive dysfunction in BD.
Identifiants
pubmed: 35969184
doi: 10.15252/embr.202154420
pmc: PMC9535808
doi:
Substances chimiques
CACNB2 protein, human
0
Cacna1c protein, rat
0
Cacnb2 protein, rat
0
Calcium Channels, L-Type
0
MIRN499 microRNA, human
0
MIRN499 microRNA, rat
0
MicroRNAs
0
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e54420Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.
Références
Hum Mol Genet. 2019 Dec 15;28(24):4113-4131
pubmed: 31628460
PLoS One. 2013;8(1):e48814
pubmed: 23382797
J Neurosci. 2017 May 3;37(18):4679-4691
pubmed: 28363979
J Vis Exp. 2014 Jun 01;(88):
pubmed: 24962249
Int J Neuropsychopharmacol. 2017 Aug 1;20(8):670-680
pubmed: 28498954
Dev Cell. 2009 Nov;17(5):662-73
pubmed: 19922871
Neuron. 2013 May 8;78(3):483-97
pubmed: 23664615
Sci STKE. 2003 Jan 21;2003(166):PE4
pubmed: 12538881
Mol Psychiatry. 2014 Aug;19(8):890-4
pubmed: 23979604
Bipolar Disord. 2015 Nov;17(7):769-80
pubmed: 26396062
Front Behav Neurosci. 2015 May 01;9:102
pubmed: 25983681
Neuroimage. 2004 Sep;23(1):84-97
pubmed: 15325355
Genome Med. 2014 Oct 10;6(10):75
pubmed: 25360157
J Psychiatry Neurosci. 2018 Oct 24;44(2):89-101
pubmed: 30354038
Mol Psychiatry. 2009 Mar;14(3):252-60
pubmed: 19065143
Mol Psychiatry. 2019 Jan;24(1):67-87
pubmed: 29679070
Science. 2009 Jul 24;325(5939):433
pubmed: 19628861
Mol Psychiatry. 2015 Feb;20(2):162-9
pubmed: 25403839
Nat Genet. 2013 Sep;45(9):984-94
pubmed: 23933821
Transl Psychiatry. 2021 May 3;11(1):263
pubmed: 33941769
Circ Res. 2012 Aug 17;111(5):521-31
pubmed: 22752967
Neurobiol Learn Mem. 2018 Nov;155:543-555
pubmed: 29800644
J Affect Disord. 2009 Feb;113(1-2):1-20
pubmed: 18684514
Mol Psychiatry. 2018 Mar;23(3):533-543
pubmed: 28696432
Mol Psychiatry. 2021 Aug;26(8):4106-4116
pubmed: 31801967
Neuron. 2000 Jan;25(1):177-90
pubmed: 10707982
Mol Autism. 2020 Jun 23;11(1):54
pubmed: 32576230
Epigenetics. 2013 Mar;8(3):317-32
pubmed: 23417056
Neurobiol Learn Mem. 2014 Jul;112:17-29
pubmed: 24113652
Learn Mem. 2009 Dec 22;17(1):5-11
pubmed: 20028732
EMBO Rep. 2022 Oct 6;23(10):e54420
pubmed: 35969184
J Thorac Dis. 2015 May;7(5):890-6
pubmed: 26101645
Nat Neurosci. 2013 Feb;16(2):201-9
pubmed: 23313911
Eur Psychiatry. 2018 Aug;52:116-125
pubmed: 29787961
Lancet Psychiatry. 2016 Apr;3(4):342-9
pubmed: 26873185
BBA Clin. 2017 Feb 09;7:78-84
pubmed: 28239561
Neuroimage. 2018 May 15;172:450-460
pubmed: 29410079
Neuropsychopharmacology. 2009 May;34(6):1395-405
pubmed: 18704095
Psychiatry Res. 2019 Aug;278:180-187
pubmed: 31207455
Nature. 2006 Jan 19;439(7074):283-9
pubmed: 16421561
EMBO J. 2011 Sep 23;30(20):4299-308
pubmed: 21946562
Cell. 2018 Mar 22;173(1):20-51
pubmed: 29570994
Nat Neurosci. 2015 May;18(5):666-73
pubmed: 25867122
Behav Brain Res. 2011 Sep 12;222(1):73-80
pubmed: 21420441
Compr Physiol. 2016 Mar 15;6(2):603-21
pubmed: 27065163
Neuron. 2002 Jun 13;34(6):999-1010
pubmed: 12086646
Proc Natl Acad Sci U S A. 2022 Feb 15;119(7):
pubmed: 35135875
Neurosci Biobehav Rev. 2008 Aug;32(6):1087-102
pubmed: 18423591
Arch Gen Psychiatry. 2010 Sep;67(9):939-45
pubmed: 20819988
J Affect Disord. 2010 Dec;127(1-3):332-6
pubmed: 20579744
Front Neural Circuits. 2010 Jan 12;3:16
pubmed: 20126250
Am J Psychiatry. 2014 Aug;171(8):829-43
pubmed: 24626773
Nat Commun. 2017 May 22;8:15497
pubmed: 28530238
Nat Neurosci. 2011 Feb;14(2):173-80
pubmed: 21186355
Psychoneuroendocrinology. 2013 Jun;38(6):927-40
pubmed: 23122890
PLoS One. 2020 Oct 27;15(10):e0240439
pubmed: 33108362
Neuroimage. 2007 Oct 15;38(1):95-113
pubmed: 17761438
J Affect Disord. 2018 Jun;233:110-116
pubmed: 28969861
J Neurosci. 2005 Oct 26;25(43):9883-92
pubmed: 16251435
Learn Mem. 2017 Oct 16;24(11):580-588
pubmed: 29038219
Am J Med. 1999 Oct;107(4):332-9
pubmed: 10527034
Sci Rep. 2020 Jan 22;10(1):993
pubmed: 31969673
J Cell Biol. 1993 Nov;123(4):949-62
pubmed: 8227151
Eur Arch Psychiatry Clin Neurosci. 2019 Dec;269(8):949-962
pubmed: 30267149
Int J Neuropsychopharmacol. 2009 Aug;12(7):975-81
pubmed: 19254429
Neuroimage. 2005 Jul 1;26(3):839-51
pubmed: 15955494
PLoS One. 2014 Jan 27;9(1):e86469
pubmed: 24475125
Cell Calcium. 2005 May;37(5):411-6
pubmed: 15820388
Nat Genet. 2021 Jun;53(6):817-829
pubmed: 34002096
Learn Mem. 2008 Jan 03;15(1):1-5
pubmed: 18174367
Dis Model Mech. 2018 Jun 20;11(6):
pubmed: 29739816
Mol Psychiatry. 2017 Aug;22(8):1096-1109
pubmed: 28584287
Nat Methods. 2014 Oct;11(10):982-4
pubmed: 25264773
Epidemiol Psychiatr Sci. 2019 Oct 25;29:e63
pubmed: 31648654
Biol Psychiatry. 2010 Nov 1;68(9):801-10
pubmed: 20723887
Transl Psychiatry. 2015 Nov 10;5:e678
pubmed: 26556287
Nat Rev Neurosci. 2009 Dec;10(12):842-9
pubmed: 19888283
J Psychopharmacol. 2016 Nov;30(11):1099-1128
pubmed: 27756833
Lancet. 2020 Dec 5;396(10265):1841-1856
pubmed: 33278937
Neurosci Lett. 2017 Jul 27;654:117-119
pubmed: 28647289
Life Sci. 2008 Jan 2;82(1-2):41-9
pubmed: 18045623
J Biol Chem. 2002 Sep 13;277(37):33598-603
pubmed: 12114507