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multimodal-world-knowledge-in-videos-enables-long-chain-reasoning-for-complex-question-answering

ビデオ理解における複雑な推論を必要とするworldqaデータセット

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evaluating-drivers-interactive-abilities-in-complex-social-scenarios-a-process-based-framework

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constructing-outerplanar-and-2-page-book-embeddings-for-degree-sequences


Knockdown of PHOX2B in the retrotrapezoid nucleus (RTN) of adult rats reduces the central CO2 chemoreflex response, likely by decreasing the expression of key CO2/pH sensors GPR4 and TASK-2 in RTN neurons.


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PHOX2B is a transcription factor essential for the development of different classes of neurons in the central and peripheral nervous system. Heterozygous mutations in the PHOX2B coding region are responsible for the occurrence of Congenital Central Hypoventilation Syndrome (CCHS), a rare neurological disorder characterised by inadequate chemosensitivity and life-threatening sleep- related hypoventilation. Animal studies suggest that chemoreflex defects are caused in part by the improper development or function of PHOX2B expressing neurons in the retrotrapezoid nucleus (RTN), a central hub for CO2 chemosensitivity.

Although the function of PHOX2B in rodents during development is well established, its role in the adult respiratory network remains unknown. In this study, we investigated whether reduction in PHOX2B expression in chemosensitive neuromedin-B (NMB) expressing neurons in the RTN altered respiratory function. Four weeks following local RTN injection of a lentiviral vector expressing the short hairpin RNA (shRNA) targeting Phox2b mRNA, a reduction of PHOX2B expression was observed in Nmb neurons compared to both naïve rats and rats injected with the non-target shRNA. PHOX2B knockdown did not affect breathing in room air or under hypoxia, but ventilation was significantly impaired during hypercapnia. PHOX2B knockdown did not alter Nmb expression but it was associated with reduced the expression of both Task2 and Gpr4 , two CO2 sensors in the RTN. We conclude that PHOX2B in the adult brain has an important role in CO2 chemoreception and reduced PHOX2B expression in CCHS beyond the developmental period may contribute to the impaired central chemoreflex function.

### Competing Interest Statement

The authors have declared no competing interest.

Knockdown of PHOX2B in the retrotrapezoid nucleus reduces the central CO2 chemoreflex in rats

knockdown-of-phox2b-in-the-retrotrapezoid-nucleus-impairs-central-co2-chemoreflex-in-rats


Knockdown of PHOX2B in the Retrotrapezoid Nucleus Impairs Central CO2 Chemoreflex in Rats


title_rewrite

Role of PHOX2B transcription factor in central CO2 chemoreception