دورية أكاديمية
Sustained chemogenetic activation of locus coeruleus norepinephrine neurons promotes dopaminergic neuron survival in synucleinopathy.
العنوان: | Sustained chemogenetic activation of locus coeruleus norepinephrine neurons promotes dopaminergic neuron survival in synucleinopathy. |
---|---|
المؤلفون: | Jovanovic P; Center for Neural Science and Medicine, Biomedical Sciences Department and Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America., Wang Y; Center for Neural Science and Medicine, Biomedical Sciences Department and Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America., Vit JP; Department of Neurosurgery, Cedars-Sinai Medical Center, Movement Disorder Program, Los Angeles, CA, United States of America., Novinbakht E; Center for Neural Science and Medicine, Biomedical Sciences Department and Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America., Morones N; Center for Neural Science and Medicine, Biomedical Sciences Department and Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America., Hogg E; Department of Neurology, Cedars-Sinai Medical Center, Movement Disorder Program, Los Angeles, CA, United States of America., Tagliati M; Department of Neurology, Cedars-Sinai Medical Center, Movement Disorder Program, Los Angeles, CA, United States of America., Riera CE; Center for Neural Science and Medicine, Biomedical Sciences Department and Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America.; Department of Neurology, Cedars-Sinai Medical Center, Movement Disorder Program, Los Angeles, CA, United States of America.; David Geffen School of Medicine, University of California, Los Angeles, CA, United States of America. |
المصدر: | PloS one [PLoS One] 2022 Mar 22; Vol. 17 (3), pp. e0263074. Date of Electronic Publication: 2022 Mar 22 (Print Publication: 2022). |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: San Francisco, CA : Public Library of Science |
مواضيع طبية MeSH: | Parkinson Disease*/pathology , Synucleinopathies*, Animals ; Disease Models, Animal ; Dopaminergic Neurons/metabolism ; Humans ; Locus Coeruleus/metabolism ; Mice ; Mice, Transgenic ; Norepinephrine/pharmacology ; Norepinephrine/physiology ; Substantia Nigra/metabolism ; alpha-Synuclein/genetics ; alpha-Synuclein/metabolism |
مستخلص: | Dopaminergic neuron degeneration in the midbrain plays a pivotal role in motor symptoms associated with Parkinson's disease. However, non-motor symptoms of Parkinson's disease and post-mortem histopathology confirm dysfunction in other brain areas, including the locus coeruleus and its associated neurotransmitter norepinephrine. Here, we investigate the role of central norepinephrine-producing neurons in Parkinson's disease by chronically stimulating catecholaminergic neurons in the locus coeruleus using chemogenetic manipulation. We show that norepinephrine neurons send complex axonal projections to the dopaminergic neurons in the substantia nigra, confirming physical communication between these regions. Furthermore, we demonstrate that increased activity of norepinephrine neurons is protective against dopaminergic neuronal depletion in human α-syn A53T missense mutation over-expressing mice and prevents motor dysfunction in these mice. Remarkably, elevated norepinephrine neurons action fails to alleviate α-synuclein aggregation and microgliosis in the substantia nigra suggesting the presence of an alternate neuroprotective mechanism. The beneficial effects of high norepinephrine neuron activity might be attributed to the action of norepinephrine on dopaminergic neurons, as recombinant norepinephrine treatment increased primary dopaminergic neuron cultures survival and neurite sprouting. Collectively, our results suggest a neuroprotective mechanism where noradrenergic neurons activity preserves the integrity of dopaminergic neurons, which prevents synucleinopathy-dependent loss of these cells. Competing Interests: The authors declare no competing interest. |
References: | J Parkinsons Dis. 2018;8(2):259-265. (PMID: 29614702) Eur J Neurosci. 2003 Jun;17(12):2586-92. (PMID: 12823465) Neurosci Biobehav Rev. 2000 Aug;24(6):655-68. (PMID: 10940440) Mol Neurodegener. 2011 Jan 21;6(1):8. (PMID: 21255396) Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8968-73. (PMID: 12084935) Nat Neurosci. 2013 Aug;16(8):1016-23. (PMID: 23852112) Mol Neurobiol. 2019 Apr;56(4):2653-2669. (PMID: 30051353) Cell Tissue Res. 2004 Oct;318(1):121-34. (PMID: 15338272) Mol Metab. 2019 Jun;24:120-138. (PMID: 30833218) J Vis Exp. 2018 Jun 5;(136):. (PMID: 29939190) J Chem Neuroanat. 1994 Aug;7(3):185-90. (PMID: 7848573) Front Neurosci. 2020 Mar 20;14:229. (PMID: 32265637) Front Neurosci. 2018 Feb 19;12:80. (PMID: 29515354) Aging Cell. 2019 Dec;18(6):e13031. (PMID: 31432604) Nat Rev Neurosci. 2017 Sep;18(9):515-529. (PMID: 28747776) Neuroscience. 1995 Dec;69(3):711-26. (PMID: 8596642) Neuroscience. 1980;5(1):21-40. (PMID: 6988734) Diabetes Metab Res Rev. 2011 Sep;27(6):604-8. (PMID: 21538777) Nature. 1997 Aug 28;388(6645):839-40. (PMID: 9278044) CNS Neurol Disord Drug Targets. 2014 Apr;13(3):418-28. (PMID: 24059307) Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3463-8. (PMID: 25733901) Science. 2000 Feb 18;287(5456):1265-9. (PMID: 10678833) Nature. 1988 Jul 28;334(6180):345-8. (PMID: 2899295) Synapse. 1998 Oct;30(2):205-10. (PMID: 9723790) Endocr Rev. 2008 Jun;29(4):494-511. (PMID: 18436709) Metabolism. 1997 Dec;46(12):1448-53. (PMID: 9439541) Acta Neuropathol Commun. 2017 Feb 1;5(1):11. (PMID: 28143577) J Neurotrauma. 2012 Jan 20;29(2):375-84. (PMID: 21561314) Nat Clin Pract Neurol. 2006 Mar;2(3):136-46. (PMID: 16932540) Neuron. 2002 May 16;34(4):521-33. (PMID: 12062037) J Neurosci Res. 2002 Oct 15;70(2):232-7. (PMID: 12271472) Antioxid Redox Signal. 2011 Apr 1;14(7):1289-301. (PMID: 20712409) PLoS One. 2019 May 29;14(5):e0216796. (PMID: 31141518) Prog Neurobiol. 2014 Jul;118:1-18. (PMID: 24582776) Psychopharmacology (Berl). 1987;92(1):1-7. (PMID: 3110818) Eur J Neurol. 2004 Apr;11(4):231-5. (PMID: 15061824) Neuroscience. 1991;41(2-3):507-23. (PMID: 1870701) J Neurochem. 2004 Dec;91(5):1116-24. (PMID: 15569255) Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13804-9. (PMID: 17702867) Science. 2010 Sep 24;329(5999):1663-7. (PMID: 20798282) Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5163-8. (PMID: 17360345) Sci Rep. 2019 Mar 27;9(1):5262. (PMID: 30918302) J Neurol Sci. 2012 Apr 15;315(1-2):39-43. (PMID: 22265943) Diabetes Care. 2011 Apr;34(4):910-5. (PMID: 21378214) Front Neurosci. 2018 Sep 11;12:626. (PMID: 30258347) Redox Biol. 2021 Apr;40:101839. (PMID: 33486153) Neurology. 2012 May 8;78(19):1507-11. (PMID: 22539572) Front Hum Neurosci. 2012 Jan 03;5:179. (PMID: 22287946) Ther Adv Neurol Disord. 2014 Jan;7(1):52-9. (PMID: 24409202) Ann Neurol. 1990 Apr;27(4):373-85. (PMID: 1972319) Antioxid Redox Signal. 2016 Apr 10;24(11):557-74. (PMID: 26866473) Brain Res. 2015 Nov 2;1625:255-74. (PMID: 26342895) Mov Disord. 2015 Feb;30(2):229-37. (PMID: 25449044) Lancet. 2017 Oct 7;390(10103):1664-1675. (PMID: 28781108) Free Radic Biol Med. 2014 Aug;73:328-36. (PMID: 24863694) J Comp Neurol. 1975 Nov 15;164(2):209-31. (PMID: 810499) Eur J Neurol. 2008 Apr;15 Suppl 1:14-20. (PMID: 18353132) J Pharmacol Exp Ther. 1994 Mar;268(3):1403-10. (PMID: 7908055) Neuron. 2016 Feb 17;89(4):683-94. (PMID: 26889809) J Parkinsons Dis. 2013;3(4):461-91. (PMID: 24252804) Protein Sci. 1993 Aug;2(8):1198-209. (PMID: 8401205) Mov Disord. 1997 Nov;12(6):871-6. (PMID: 9399209) J Neurol Neurosurg Psychiatry. 1960 Nov;23:283-90. (PMID: 13711997) Arch Neurol. 2006 Dec;63(12):1724-8. (PMID: 17172611) Curr Biol. 2015 Nov 2;25(21):R1051-R1056. (PMID: 26528750) Front Neuroanat. 2017 Nov 02;11:98. (PMID: 29163071) Cold Spring Harb Perspect Med. 2012 Feb;2(2):a009399. (PMID: 22355802) J Neurochem. 2001 Oct;79(1):200-10. (PMID: 11595772) |
المشرفين على المادة: | 0 (alpha-Synuclein) X4W3ENH1CV (Norepinephrine) |
تواريخ الأحداث: | Date Created: 20220322 Date Completed: 20220414 Latest Revision: 20220531 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC8939823 |
DOI: | 10.1371/journal.pone.0263074 |
PMID: | 35316276 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1932-6203 |
---|---|
DOI: | 10.1371/journal.pone.0263074 |