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AMPK phosphorylates LMX1b to regulate a brainstem neurogenic network important for control of breathing in neonatal mice

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Ventilatory drive is modulated by a variety of neurochemical inputs that converge on spatially oriented clusters of cells within the brainstem. This regulation is required to maintain energy homeostasis and is essential to sustain life across all mammalian organisms. However, the mechanistic understanding of the regulation of these ventilatory control cellular clusters is poorly defined. This study explores the role of AMP-activated protein kinase (AMPK) and LIM homeobox transcription factor 1-beta (Lmx1b), a key player in dorsal-ventral patterning during fetal development, in the regulation of brainstem ventilatory control centers Brain stem tissue was isolated from AMPK+/+, AMPK-/-, LMX1B+/+, LMX1B+/-, or LMX1B-/- C57BL/6 mice and RNA sequencing expression profiling was performed.

呼吸驱动受多种神经化学输入调控,这些输入会聚于脑干内空间定位的细胞簇。该调控过程对于维持能量稳态必不可少,亦是所有哺乳动物机体维持生命的关键环节。然而,目前对于此类呼吸调控细胞簇的调控机制仍尚不明确。本研究探讨了AMP活化蛋白激酶(AMP-activated protein kinase,AMPK)以及胎儿发育过程中背腹模式形成的关键调控因子LIM同源盒转录因子1-β(LIM homeobox transcription factor 1-beta,Lmx1b)在脑干呼吸调控中枢的调控中的作用。研究人员从AMPK+/+、AMPK-/-、LMX1B+/+、LMX1B+/-或LMX1B-/- C57BL/6小鼠中分离脑干组织,并开展了RNA测序表达谱分析。

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