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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The role of PHOX2B-derived astrocytes in chemosensory control of breathing and sleep homeostasis

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Author(s):
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Czeisler, Catherine M. [1] ; Silva, Talita M. [2] ; Fair, Summer R. [1] ; Liu, Jillian [1] ; Tupal, Srinivasan [1] ; Kaya, Behiye [1] ; Cowgill, Aaron [1] ; Mahajan, Salil [1] ; Silva, Phelipe E. [2] ; Wang, Yangyang [3, 4] ; Blissett, Angela R. [5] ; Goksel, Mustafa [1] ; Borniger, Jeremy C. [3] ; Zhang, Ning [6] ; Fernandes-Junior, Silvio A. [7, 8] ; Catacutan, Fay [1] ; Alves, Michele J. [1] ; Nelson, Randy J. [6] ; Sundaresean, Vishnu [1] ; Rekling, Jens [9] ; Takakura, Ana C. [7] ; Moreira, Thiago S. [2] ; Otero, Jose J. [1]
Total Authors: 23
Affiliation:
[1] Ohio State Univ, Coll Med, Dept Pathol, 4169 Graves Hall, 333 W 10th Ave, Columbus, OH 43210 - USA
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, 1524 Prof Lineu Prestes Ave, BR-05508 Sao Paulo, SP - Brazil
[3] Ohio State Univ, Coll Med, Dept Neurosci, Columbus, OH 43210 - USA
[4] Ohio State Univ, Math Biosci Inst, Columbus, OH 43210 - USA
[5] Ohio State Univ, Coll Engn, Dept Mech & Aerosp Engn, Columbus, OH 43210 - USA
[6] West Virginia Univ, Dept Neurosci, Morgantown, WV 26506 - USA
[7] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil
[8] Ohio State Univ, Campus Microscopy & Imaging Facil, Columbus, OH 43210 - USA
[9] Univ Copenhagen, Dept Neurosci, Copenhagen - Denmark
Total Affiliations: 9
Document type: Journal article
Source: JOURNAL OF PHYSIOLOGY-LONDON; v. 597, n. 8, p. 2225-2251, APR 15 2019.
Web of Science Citations: 4
Abstract

We identify in mice a population of approximate to 800 retrotrapezoid nucleus (RTN) astrocytes derived from PHOX2B-positive, OLIG3-negative progenitor cells, that interact with PHOX2B-expressing RTN chemosensory neurons. PHOX2B-derived astrocyte ablation during early life results in adult-onset O-2 chemoreflex deficiency. These animals also display changes in sleep homeostasis, including fragmented sleep and disturbances in delta power after sleep deprivation, all without observable changes in anxiety or social behaviours. Ultrastructural evaluation of the RTN demonstrates that PHOX2B-derived astrocyte ablation results in features characteristic of degenerative neuro-axonal dystrophy, including abnormally dilated axon terminals and increased amounts of synapses containing autophagic vacuoles/phagosomes. We conclude that PHOX2B-derived astrocytes are necessary for maintaining a functional O-2 chemosensory reflex in the adult, modulate sleep homeostasis, and are key regulators of synaptic integrity in the RTN region, which is necessary for the chemosensory control of breathing. These data also highlight how defects in embryonic development may manifest as neurodegenerative pathology in an adult. (AU)

FAPESP's process: 15/23376-1 - Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity
Grantee:Thiago dos Santos Moreira
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 16/23281-3 - Encephalic regions responsible for neuroplasticity observed in respiratory response induced by hypercapnia in a modelo of Parkinson's Disease
Grantee:Ana Carolina Takakura Moreira
Support Opportunities: Regular Research Grants
FAPESP's process: 16/22069-0 - Amelioration of the brainstem vascular imbalances in an spontaneously hypertensive rats with exercise
Grantee:Thiago dos Santos Moreira
Support Opportunities: Regular Research Grants