Microarray profiling of hypothalamic gene expression changes in Huntington's disease mouse models.
HD mouse models
Huntington’s disease
differential expression
huntingtin
hypothalamus
microarray
neuroendocrine
Journal
Frontiers in neuroscience
ISSN: 1662-4548
Titre abrégé: Front Neurosci
Pays: Switzerland
ID NLM: 101478481
Informations de publication
Date de publication:
2022
2022
Historique:
received:
24
08
2022
accepted:
10
10
2022
entrez:
21
11
2022
pubmed:
22
11
2022
medline:
22
11
2022
Statut:
epublish
Résumé
Structural changes and neuropathology in the hypothalamus have been suggested to contribute to the non-motor manifestations of Huntington's disease (HD), a neurodegenerative disorder caused by an expanded cytosine-adenine-guanine (CAG) repeat in the huntingtin (HTT) gene. In this study, we investigated whether hypothalamic HTT expression causes transcriptional changes. Hypothalamic RNA was isolated from two different HD mouse models and their littermate controls; BACHD mice with ubiquitous expression of full-length mutant HTT (mHTT) and wild-type mice with targeted hypothalamic overexpression of either wild-type HTT (wtHTT) or mHTT fragments. The mHTT and wtHTT groups showed the highest number of differentially expressed genes compared to the BACHD mouse model. Gene Set Enrichment Analysis (GSEA) with leading-edge analysis showed that suppressed sterol- and cholesterol metabolism were shared between hypothalamic wtHTT and mHTT overexpression. Most distinctive for mHTT overexpression was the suppression of neuroendocrine networks, in which qRT-PCR validation confirmed significant downregulation of neuropeptides with roles in feeding behavior; hypocretin neuropeptide precursor (
Identifiants
pubmed: 36408416
doi: 10.3389/fnins.2022.1027269
pmc: PMC9671106
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1027269Informations de copyright
Copyright © 2022 Dickson, Dwijesha, Andersson, Lundh, Björkqvist, Petersén and Soylu-Kucharz.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Neurology. 2009 Aug 4;73(5):385-92
pubmed: 19652143
PLoS One. 2013 Dec 20;8(12):e83050
pubmed: 24376631
Nucleic Acids Res. 2022 Mar 23;:
pubmed: 35325185
J Neurosci. 2021 Jun 23;41(25):5534-5552
pubmed: 34011527
Am J Hum Genet. 1997 May;60(5):1202-10
pubmed: 9150168
J Huntingtons Dis. 2019;8(4):375-391
pubmed: 31594240
Nat Rev Dis Primers. 2015 Apr 23;1:15005
pubmed: 27188817
Neurobiol Dis. 2008 Jan;29(1):41-51
pubmed: 17920283
Nat Rev Neurosci. 2005 Dec;6(12):919-30
pubmed: 16288298
Biol Psychiatry. 2007 Dec 15;62(12):1341-6
pubmed: 17481592
J Clin Lipidol. 2010 Jan-Feb;4(1):17-23
pubmed: 20802793
Nat Rev Neurol. 2015 Jul;11(7):401-13
pubmed: 26100750
Hum Mol Genet. 2006 May 1;15(9):1513-23
pubmed: 16571604
Front Endocrinol (Lausanne). 2021 Sep 21;12:731966
pubmed: 34671318
Nutrition. 2004 Feb;20(2):192-6
pubmed: 14962685
Innovation (Camb). 2021 Jul 01;2(3):100141
pubmed: 34557778
Cell Metab. 2011 Apr 6;13(4):428-439
pubmed: 21459327
Neurobiol Dis. 2010 Dec;40(3):531-43
pubmed: 20682340
J Neurosci. 2005 Oct 26;25(43):9932-9
pubmed: 16251441
Arch Neurol. 2008 Apr;65(4):476-80
pubmed: 18413469
Curr Opin Endocrinol Diabetes Obes. 2015 Oct;22(5):325-30
pubmed: 26192704
Nucleic Acids Res. 2002 Jan 1;30(1):207-10
pubmed: 11752295
Med J Aust. 1981 Apr 18;1(8):407-9
pubmed: 6454826
J Neurochem. 2005 May;93(3):641-53
pubmed: 15836623
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Yale J Biol Med. 1951 Nov;24(2):123-40
pubmed: 14901884
Am J Hum Genet. 1996 Jul;59(1):16-22
pubmed: 8659522
Cell Rep. 2014 Dec 24;9(6):2124-38
pubmed: 25497089
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
Bioinformatics. 2004 Feb 12;20(3):307-15
pubmed: 14960456
PLoS One. 2012;7(9):e44544
pubmed: 23028558
Sci Rep. 2015 Sep 30;5:14598
pubmed: 26419281
Nat Rev Neurosci. 2013 Jul;14(7):472-87
pubmed: 23783198
J Neurosci Res. 2006 Nov 1;84(6):1151-64
pubmed: 16983659
Biol Psychiatry. 2016 Feb 1;79(3):174-84
pubmed: 26392129
J Neurosci. 2002 May 1;22(9):3473-83
pubmed: 11978824
Neurol Genet. 2021 Jul 06;7(4):e603
pubmed: 34250226
J Biol Chem. 2015 Oct 30;290(44):26383-92
pubmed: 26370080
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Brain Pathol. 2008 Oct;18(4):474-83
pubmed: 18498421
Hum Mol Genet. 2010 Apr 15;19(8):1528-38
pubmed: 20097678
Ann Appl Stat. 2016 Jun;10(2):946-963
pubmed: 28367255
Prog Neurobiol. 2007 Apr;81(5-6):253-71
pubmed: 17169479
J Biol Chem. 1973 Oct 10;248(19):6796-809
pubmed: 4745444
J Neurol Neurosurg Psychiatry. 2004 Feb;75(2):213-20
pubmed: 14742591
Nucleic Acids Res. 2012 Aug;40(15):e115
pubmed: 22730293
N Engl J Med. 2019 Jun 13;380(24):2307-2316
pubmed: 31059641
Front Neurosci. 2020 Feb 06;14:82
pubmed: 32116525
Neuron. 2016 Mar 2;89(5):910-26
pubmed: 26938440
Lancet Neurol. 2009 Aug;8(8):765-74
pubmed: 19608102
Hum Mol Genet. 2001 Jan 15;10(2):145-52
pubmed: 11152662
Hum Mol Genet. 2005 Jan 15;14(2):179-89
pubmed: 15548548
Neuroendocrinology. 2006;83(5-6):289-94
pubmed: 16926531
Behav Brain Res. 1995 Dec 14;72(1-2):83-8
pubmed: 8788860
Brain Res. 2011 Jan 7;1367:130-45
pubmed: 20869353
Ann Neurol. 2017 Sep;82(3):479-483
pubmed: 28779551
Hum Mol Genet. 2013 Sep 1;22(17):3485-97
pubmed: 23697793
Physiol Rev. 2012 Jul;92(3):1087-187
pubmed: 22811426
N Engl J Med. ;376(15):1491-2
pubmed: 28406283
Neurobiol Dis. 2019 Dec;132:104560
pubmed: 31419548
Nucleic Acids Res. 2016 Jan 4;44(D1):D457-62
pubmed: 26476454
Synapse. 2016 Mar;70(3):71-86
pubmed: 26695835
Protein Cell. 2015 Apr;6(4):254-64
pubmed: 25682154
Neuropathol Appl Neurobiol. 2019 Jun;45(4):361-379
pubmed: 30019499
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Mol Metab. 2022 Mar;57:101439
pubmed: 35007790
J Neurosci. 2008 Jun 11;28(24):6182-95
pubmed: 18550760
Brain. 2008 Nov;131(Pt 11):2860-9
pubmed: 18829696
PLoS One. 2007 Jul 25;2(7):e647
pubmed: 17653274
Trends Neurosci. 2015 Jan;38(1):26-35
pubmed: 25282404
Glia. 2014 Jan;62(1):17-25
pubmed: 24166765
Front Cell Neurosci. 2021 Jun 15;15:689332
pubmed: 34211373
Front Neurosci. 2013 Jul 04;7:114
pubmed: 23847463
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):E2253-E2262
pubmed: 28246328
Cell. 1993 Mar 26;72(6):971-83
pubmed: 8458085
Neurology. 2002 Nov 12;59(9):1325-30
pubmed: 12427878
Neuroscience. 1999;94(4):1279-90
pubmed: 10625067
Arch Neurol. 2001 Feb;58(2):273-8
pubmed: 11176966
Hum Mol Genet. 2005 Jan 1;14(1):39-47
pubmed: 15525658
J Clin Invest. 2017 Jan 3;127(1):24-32
pubmed: 28045396
Pharmacol Res Perspect. 2015 Feb;3(1):e00104
pubmed: 25692022
Hum Mol Genet. 2002 Aug 15;11(17):1953-65
pubmed: 12165557
Cell Metab. 2015 Dec 1;22(6):962-70
pubmed: 26603190
Gene Ther. 2003 Jun;10(11):935-40
pubmed: 12756413
Lancet Neurol. 2017 Oct;16(10):837-847
pubmed: 28920889
Trends Neurosci. 2010 Nov;33(11):513-23
pubmed: 20850189
Brain Pathol. 2011 Jul;21(4):419-27
pubmed: 21106039
Physiol Behav. 1988;44(2):221-6
pubmed: 3237828