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

Autor(es):Mostrar menos -

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PHYSIOLOGY-LONDON; v. 597, n. 8, p. 2225-2251, APR 15 2019.
• Citações Web of Science: 4

Resumo

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)

• Processo FAPESP: 17/12678-2 - Participação dos astrócitos localizados na superfície ventrolateral do bulbo nas respostas ventilatórias à hipercapnia e hipóxia
• Beneficiário: Talita de Melo e Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/23376-1 - Núcleo retrotrapezóide, quimiossensibilidade central e automaticidade respiratória
• Beneficiário: Thiago dos Santos Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/23281-3 - Regiões encefálicas responsáveis pela neuroplasticidade observada na resposta respiratória induzida por hipercapnia em modelo animal de Doença de Parkinson
• Beneficiário: Ana Carolina Takakura Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/22069-0 - Melhora nos mecanismos de regulação do fluxo sanguíneo encefálico em animais espontaneamente hipertensos: participação do exercício físico
• Beneficiário: Thiago dos Santos Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular