{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:42:01Z","timestamp":1760146921860,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Loma Linda University School of Medicine","award":["NIH NICHD HD092941-01 (R21)"],"award-info":[{"award-number":["NIH NICHD HD092941-01 (R21)"]}]},{"name":"U.S. National Institutes of Health (NICHD)","award":["NIH NICHD HD092941-01 (R21)"],"award-info":[{"award-number":["NIH NICHD HD092941-01 (R21)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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. Therefore, the anatomical orientation of these cellular clusters during development must have a defined mechanistic basis with redundant genomic variants. Failure to completely develop these features causes several conditions including apnea of prematurity (AOP) and sudden infant death syndrome (SIDS). AOP is associated with many adverse outcomes including increased risk of interventricular hemorrhage. However, there are no pharmacological interventions that reduce SIDS and AOP prevalence by promoting brainstem development. AMP-activated protein kinase (AMPK) is a kinase that regulates ventilatory control to maintain homeostasis. This study identifies a signaling axis in which the pharmacological activation of AMPK in vivo via metformin in brainstem ventilatory control centers results in the phosphorylation of LIM homeobox transcription factor 1-beta (Lmx1b), a key player in dorsal\u2013ventral patterning during fetal development. The phosphorylation of Lmx1b transactivates a neurogenic interactome important for the development and regulation of ventilatory control centers. These findings highlight the potential for metformin in the treatment and prevention of AOP.<\/jats:p>","DOI":"10.3390\/ijms26010213","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T07:51:57Z","timestamp":1735631517000},"page":"213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["AMPK Phosphorylates LMX1b to Regulate a Brainstem Neurogenic Network Important for Control of Breathing in Neonatal Mice"],"prefix":"10.3390","volume":"26","author":[{"given":"Traci L.","family":"Marin","sequence":"first","affiliation":[{"name":"Department of Respiratory Therapy, Victor Valley College, Victorville, CA 92395, USA"},{"name":"Department of Medicine, University of California San Diego, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher G.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, Division of Physiology, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel Lopez","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, San Diego, CA 92093, USA"},{"name":"Department of Pharmacology, University of California San Diego, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, San Diego, CA 92093, USA"},{"name":"VA San Deigo Medical Center, San Diego, CA 92161, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9509-1827","authenticated-orcid":false,"given":"Atul","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brendan","family":"Gongol","sequence":"additional","affiliation":[{"name":"Department of Respiratory Therapy, Victor Valley College, Victorville, CA 92395, USA"},{"name":"Institute for Integrative Genome Biology, University of California, Riverside, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/S0140-6736(23)00878-4","article-title":"National, regional, and global estimates of preterm birth in 2020, with trends from 2010: A systematic analysis","volume":"402","author":"Ohuma","year":"2023","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e20153757","DOI":"10.1542\/peds.2015-3757","article-title":"Committee on Fetus and Newborn; American Academy of Pediatrics. 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