دورية أكاديمية
أعرض في EDS

Sustained chemogenetic activation of locus coeruleus norepinephrine neurons promotes dopaminergic neuron survival in synucleinopathy.

التفاصيل البيبلوغرافية
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.
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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
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0263074