小柯机器人

一种大脑产生的多肽能够支持出生后的第一次呼吸
2020-12-03 14:02

美国维吉尼亚大学Douglas A. Bayliss小组发现,出生时激活的脑干多肽系统可促进产后呼吸。2020年12月2日,国际知名学术期刊《自然》在线发表了这一成果。

研究人员确定了一个神经肽系统,该系统在出生后立即被激活并支持呼吸。在梯形后核(RTN)神经元中选择性缺乏PACAP的小鼠表现出呼吸暂停增加和CO2刺激的呼吸减弱。RTN神经元中PACAP的重新表达纠正了这些呼吸不足。从pre-Bötzinger复合体(一个负责产生呼吸节律的RTN目标区域)中删除PACAP受体PAC1,显著复制了RTN缺失PACAP后观察到的呼吸不足,并抑制了pre-Bötzinger复合体中PACAP诱发的呼吸刺激。值得注意的是,恰好在出生时,RTN神经元中发生了PACAP表达的产后爆发,这与暴露于外部环境相吻合。RTN神经元中PACAP缺失的新生小鼠表现出呼吸暂停增加,环境温度的变化进一步加剧了呼吸暂停。

这些发现表明,RTN神经元适时的PACAP表达在出生后立即提供了重要的辅助呼吸驱动,并揭示了在生命中最为脆弱时期支持呼吸的肽能神经回路。

研究人员介绍,在产后生命最初遇到的众多挑战中,最重要的是第一次呼吸,这会引发维持生命的运动。调节呼吸的神经系统在发育的早期是脆弱的,尚不清楚它们如何调节来支持出生时的呼吸。

附:英文原文

Title: A brainstem peptide system activated at birth protects postnatal breathing

Author: Yingtang Shi, Daniel S. Stornetta, Robert J. Reklow, Alisha Sahu, Yvonne Wabara, Ashley Nguyen, Keyong Li, Yong Zhang, Edward Perez-Reyes, Rachel A. Ross, Bradford B. Lowell, Ruth L. Stornetta, Gregory D. Funk, Patrice G. Guyenet, Douglas A. Bayliss

Issue&Volume: 2020-12-02

Abstract: Among numerous challenges encountered at the beginning of extrauterine life, the most celebrated is the first breath that initiates a life-sustaining motor activity1. The neural systems that regulate breathing are fragile early in development, and it is not clear how they adjust to support breathing at birth. Here we identify a neuropeptide system that becomes activated immediately after birth and supports breathing. Mice that lack PACAP selectively in neurons of the retrotrapezoid nucleus (RTN) displayed increased apnoeas and blunted CO2-stimulated breathing; re-expression of PACAP in RTN neurons corrected these breathing deficits. Deletion of the PACAP receptor PAC1 from the pre-Btzinger complex—an RTN target region responsible for generating the respiratory rhythm—phenocopied the breathing deficits observed after RTN deletion of PACAP, and suppressed PACAP-evoked respiratory stimulation in the pre-Btzinger complex. Notably, a postnatal burst of PACAP expression occurred in RTN neurons precisely at the time of birth, coinciding with exposure to the external environment. Neonatal mice with deletion of PACAP in RTN neurons displayed increased apnoeas that were further exacerbated by changes in ambient temperature. Our findings demonstrate that well-timed PACAP expression by RTN neurons provides an important supplementary respiratory drive immediately after birth and reveal key molecular components of a peptidergic neural circuit that supports breathing at a particularly vulnerable period in life.

DOI: 10.1038/s41586-020-2991-4

Source: https://www.nature.com/articles/s41586-020-2991-4

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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