Division of Neonatology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Pediatr Res. 2023 Sep;94(3):971-978. doi: 10.1038/s41390-023-02604-3. Epub 2023 Apr 25.
Leptin augments central CO chemosensitivity and stabilizes breathing in adults. Premature infants have unstable breathing and low leptin levels. Leptin receptors are on CO sensitive neurons in the Nucleus Tractus Solitarius (NTS) and locus coeruleus (LC). We hypothesized that exogenous leptin improves hypercapnic respiratory response in newborn rats by improving central CO chemosensitivity.
In rats at postnatal day (p)4 and p21, hyperoxic and hypercapnic ventilatory responses, and pSTAT and SOCS3 protein expression in the hypothalamus, NTS and LC were measured before and after treatment with exogenous leptin (6 µg/g).
Exogenous leptin increased the hypercapnic response in p21 but not in p4 rats (P ≤ 0.001). At p4, leptin increased pSTAT expression only in the LC, and SOCS3 expression in the NTS and LC; while at p21 pSTAT and SOCS3 levels were higher in the hypothalamus, NTS, and LC (P ≤ 0.05).
We describe the developmental profile of the effect of exogenous leptin on CO chemosensitivity. Exogenous leptin does not augment central CO sensitivity during the first week of life in newborn rats. The translational implication of these findings is that low plasma leptin levels in premature infants may not be contributing to respiratory instability.
Exogenous leptin does not augment CO sensitivity during the first week of life in newborn rats, similar to the developmental period when feeding behavior is resistant to leptin. Exogenous leptin increases CO chemosensitivity in newborn rats after the 3rd week of life and upregulates the expression of pSTAT and SOC3 in the hypothalamus, NTS and LC. Low plasma leptin levels in premature infants are unlikely contributors to respiratory instability via decreased CO sensitivity in premature infants. Thus, it is highly unlikely that exogenous leptin would alter this response.
瘦素增强了中枢 CO 敏感性，并稳定了成人的呼吸。早产儿呼吸不稳定，瘦素水平较低。瘦素受体位于孤束核（NTS）和蓝斑核（LC）中的 CO 敏感神经元上。我们假设外源性瘦素通过改善中枢 CO 敏感性来改善新生大鼠的高碳酸血症呼吸反应。
在出生后第 4 天（p4）和第 21 天（p21）的大鼠中，在给予外源性瘦素（6μg/g）前后测量高氧和高碳酸通气反应，以及下丘脑、NTS 和 LC 中的 pSTAT 和 SOCS3 蛋白表达。
外源性瘦素仅在 p21 而非 p4 大鼠中增加了高碳酸血症反应（P≤0.001）。在 p4 时，瘦素仅增加 LC 中的 pSTAT 表达，以及 NTS 和 LC 中的 SOCS3 表达；而在 p21 时，下丘脑、NTS 和 LC 中的 pSTAT 和 SOCS3 水平更高（P≤0.05）。
我们描述了外源性瘦素对 CO 敏感性的影响的发育特征。外源性瘦素在新生大鼠生命的第一周内不会增强中枢 CO 敏感性。这些发现的转化意义是，早产儿血浆瘦素水平低可能不会导致呼吸不稳定。
外源性瘦素在新生大鼠生命的第一周内不会增强 CO 敏感性，类似于对瘦素产生抵抗的喂养行为的发育时期。外源性瘦素在新生大鼠出生后第 3 周增加 CO 敏感性，并在上调下丘脑、NTS 和 LC 中的 pSTAT 和 SOC3 表达。早产儿血浆瘦素水平低不太可能通过降低早产儿的 CO 敏感性导致呼吸不稳定。因此，外源性瘦素不太可能改变这种反应。
