دورية أكاديمية
أعرض في EDS

Sterol dysregulation in Smith-Lemli-Opitz syndrome causes astrocyte immune reactivity through microglia crosstalk.

التفاصيل البيبلوغرافية
العنوان: Sterol dysregulation in Smith-Lemli-Opitz syndrome causes astrocyte immune reactivity through microglia crosstalk.
المؤلفون: Freel BA; Basic Biomedical Sciences, University of South Dakota, Vermillion, SD 57069, USA.; Cellular Therapies and Stem Cell Biology Group, Sanford Research, Sioux Falls, SD 57104, USA., Kelvington BA; Cellular Therapies and Stem Cell Biology Group, Sanford Research, Sioux Falls, SD 57104, USA., Sengupta S; Cellular Therapies and Stem Cell Biology Group, Sanford Research, Sioux Falls, SD 57104, USA., Mukherjee M; Functional Genomics and Bioinformatics Core, Sanford Research, Sioux Falls, SD 57104, USA., Francis KR; Cellular Therapies and Stem Cell Biology Group, Sanford Research, Sioux Falls, SD 57104, USA.; Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD 57105, USA.
المصدر: Disease models & mechanisms [Dis Model Mech] 2022 Dec 01; Vol. 15 (12). Date of Electronic Publication: 2022 Dec 16.
نوع المنشور: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Company of Biologists Ltd Country of Publication: England NLM ID: 101483332 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1754-8411 (Electronic) Linking ISSN: 17548403 NLM ISO Abbreviation: Dis Model Mech Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge : Company of Biologists Ltd., c2008-
مواضيع طبية MeSH: Smith-Lemli-Opitz Syndrome*/genetics , Smith-Lemli-Opitz Syndrome*/metabolism , Smith-Lemli-Opitz Syndrome*/pathology, Animals ; Mice ; Sterols ; Microglia/pathology ; Cholesterol ; Phenotype
مستخلص: Owing to the need for de novo cholesterol synthesis and cholesterol-enriched structures within the nervous system, cholesterol homeostasis is critical to neurodevelopment. Diseases caused by genetic disruption of cholesterol biosynthesis, such as Smith-Lemli-Opitz syndrome, which is caused by mutations in 7-dehydrocholesterol reductase (DHCR7), frequently result in broad neurological deficits. Although astrocytes regulate multiple neural processes ranging from cell migration to network-level communication, immunological activation of astrocytes is a hallmark pathology in many diseases. However, the impact of DHCR7 on astrocyte function and immune activation remains unknown. We demonstrate that astrocytes from Dhcr7 mutant mice display hallmark signs of reactivity, including increased expression of glial fibrillary acidic protein (GFAP) and cellular hypertrophy. Transcript analyses demonstrate extensive Dhcr7 astrocyte immune activation, hyper-responsiveness to glutamate stimulation and altered calcium flux. We further determine that the impacts of Dhcr7 are not astrocyte intrinsic but result from non-cell-autonomous effects of microglia. Our data suggest that astrocyte-microglia crosstalk likely contributes to the neurological phenotypes observed in disorders of cholesterol biosynthesis. Additionally, these data further elucidate a role for cholesterol metabolism within the astrocyte-microglia immune axis, with possible implications in other neurological diseases.
Competing Interests: Competing interests The authors declare no competing or financial interests.
(© 2022. Published by The Company of Biologists Ltd.)
References: Acta Neuropathol. 2010 Jan;119(1):7-35. (PMID: 20012068)
Brain Res. 1998 Dec 14;814(1-2):13-25. (PMID: 9838024)
Dis Model Mech. 2012 Nov;5(6):746-55. (PMID: 23065638)
Nat Neurosci. 2019 Dec;22(12):2087-2097. (PMID: 31768052)
Neurobiol Dis. 2006 Jan;21(1):154-64. (PMID: 16061389)
Neuroimage. 2012 Jan 2;59(1):565-72. (PMID: 21851856)
J Lipid Res. 2010 Nov;51(11):3259-69. (PMID: 20702862)
J Neurosci. 2010 Mar 24;30(12):4508-14. (PMID: 20335488)
Am J Med Genet B Neuropsychiatr Genet. 2006 Sep 5;141B(6):666-8. (PMID: 16874769)
Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):E302-E309. (PMID: 29279367)
Front Immunol. 2020 Aug 20;11:1818. (PMID: 32973758)
Cells. 2019 Feb 20;8(2):. (PMID: 30791579)
Acta Neuropathol Commun. 2018 Oct 16;6(1):104. (PMID: 30322407)
Nat Med. 2020 Jan;26(1):131-142. (PMID: 31932797)
Acta Neuropathol Commun. 2020 Feb 18;8(1):19. (PMID: 32070434)
Nature. 2017 Jan 26;541(7638):481-487. (PMID: 28099414)
Cell Rep. 2021 Nov 16;37(7):110008. (PMID: 34788623)
Neuropsychopharmacology. 2017 Jan;42(1):193-215. (PMID: 27629368)
Biochim Biophys Acta. 2011 May;1813(5):984-91. (PMID: 21118669)
Hum Mol Genet. 2001 Mar 15;10(6):555-64. (PMID: 11230174)
Cerebellum. 2005;4(3):206-10. (PMID: 16147953)
Cell. 2022 Jun 23;185(13):2213-2233.e25. (PMID: 35750033)
Front Pharmacol. 2012 Jul 13;3:139. (PMID: 22811669)
Elife. 2015 Jun 26;4:e07999. (PMID: 26114596)
J Pediatr. 1964 Feb;64:210-7. (PMID: 14119520)
Nature. 2021 Nov;599(7883):102-107. (PMID: 34616039)
Neuroscientist. 2019 Jun;25(3):227-240. (PMID: 29931997)
Prog Lipid Res. 2011 Oct;50(4):357-71. (PMID: 21741992)
J Neurosci. 2012 May 2;32(18):6391-410. (PMID: 22553043)
Cell. 2015 Aug 27;162(5):1170-1170.e1. (PMID: 26317476)
Hum Mol Genet. 2006 Mar 15;15(6):839-51. (PMID: 16446309)
Front Cell Neurosci. 2020 Aug 06;14:198. (PMID: 32848611)
Expert Opin Orphan Drugs. 2015 Mar;3(3):267-280. (PMID: 25734025)
Immunity. 2017 Jun 20;46(6):957-967. (PMID: 28636962)
Front Neurosci. 2020 May 20;14:444. (PMID: 32508567)
Curr Opin Clin Nutr Metab Care. 2009 Mar;12(2):152-8. (PMID: 19202386)
Am J Med Genet A. 2013 Oct;161A(10):2407-19. (PMID: 23918729)
J Neurosci. 2016 Jan 13;36(2):577-89. (PMID: 26758846)
Trends Neurosci. 2009 Dec;32(12):638-47. (PMID: 19782411)
Arterioscler Thromb Vasc Biol. 2004 May;24(5):806-15. (PMID: 14764421)
Neuron. 2016 Jan 6;89(1):37-53. (PMID: 26687838)
J Steroid Biochem Mol Biol. 2014 Mar;140:7-16. (PMID: 24269243)
Acta Neuropathol Commun. 2017 Oct 17;5(1):74. (PMID: 29041969)
J Neuroinflammation. 2020 Jul 31;17(1):227. (PMID: 32736565)
J Lipid Res. 2013 Apr;54(4):1135-43. (PMID: 23381570)
J Lipid Res. 1980 Mar;21(3):364-76. (PMID: 7189770)
Nat Neurosci. 2021 Jan;24(1):47-60. (PMID: 33349711)
Sci Transl Med. 2019 Oct 16;11(514):. (PMID: 31619545)
Elife. 2018 Mar 29;7:. (PMID: 29595472)
Nat Neurosci. 2016 Feb;19(2):182-9. (PMID: 26814587)
J Biol Chem. 2004 Aug 13;279(33):34388-96. (PMID: 15187084)
Nat Rev Neurosci. 2013 May;14(5):311-21. (PMID: 23595014)
Transl Psychiatry. 2021 Sep 9;11(1):471. (PMID: 34504056)
Nat Rev Immunol. 2018 Apr;18(4):225-242. (PMID: 29151590)
Ann Neurol. 2005 Jan;57(1):67-81. (PMID: 15546155)
Nat Med. 2016 Apr;22(4):388-96. (PMID: 26998835)
Mol Med Rep. 2018 Jul;18(1):1058-1066. (PMID: 29845194)
Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):E1896-E1905. (PMID: 29437957)
Nat Neurosci. 2021 Mar;24(3):312-325. (PMID: 33589835)
Int J Mol Sci. 2019 Feb 25;20(4):. (PMID: 30823575)
Glia. 2005 Jun;50(4):427-434. (PMID: 15846805)
Hum Mol Genet. 2010 Apr 1;19(7):1347-57. (PMID: 20067919)
Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):7285-90. (PMID: 26060301)
Glia. 2022 Apr;70(4):712-727. (PMID: 34958493)
EMBO Rep. 2014 Oct;15(10):1036-52. (PMID: 25223281)
Front Immunol. 2020 Jul 16;11:1416. (PMID: 32765501)
Neurochem Int. 2000 Aug-Sep;37(2-3):163-70. (PMID: 10812201)
ACS Chem Neurosci. 2019 Aug 21;10(8):3671-3681. (PMID: 31244054)
Stem Cell Reports. 2018 Mar 13;10(3):1030-1045. (PMID: 29456185)
J Neuroinflammation. 2017 Aug 23;14(1):167. (PMID: 28835272)
Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):1189-1194. (PMID: 28096339)
Nature. 1994 Jun 30;369(6483):744-7. (PMID: 7911978)
Front Aging Neurosci. 2022 Feb 16;14:815347. (PMID: 35250543)
J Neuroimmunol. 2018 Mar 15;316:56-64. (PMID: 29361314)
Nature. 2013 Dec 19;504(7480):394-400. (PMID: 24270812)
Mediators Inflamm. 2017;2017:2582745. (PMID: 28546657)
Arterioscler Thromb Vasc Biol. 2016 Jul;36(7):1305-15. (PMID: 27174096)
J Neurosci. 2016 Jul 6;36(27):7079-94. (PMID: 27383586)
J Lipid Res. 2021;62:100002. (PMID: 33410752)
معلومات مُعتمدة: P20 GM103548 United States GM NIGMS NIH HHS; P20 GM103620 United States GM NIGMS NIH HHS; R25 HD097633 United States HD NICHD NIH HHS
فهرسة مساهمة: Keywords: Dhcr7; Astrocyte; Cholesterol; Microglia; Reactivity; Smith–Lemli–Opitz syndrome
المشرفين على المادة: 0 (Sterols)
97C5T2UQ7J (Cholesterol)
تواريخ الأحداث: Date Created: 20221216 Date Completed: 20221219 Latest Revision: 20231119
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10655813
DOI: 10.1242/dmm.049843
PMID: 36524414
قاعدة البيانات: MEDLINE
الوصف
تدمد:1754-8411
DOI:10.1242/dmm.049843