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Maturational effect of leptin on CO 2 chemosensitivity in newborn rats.

Authors :: Tamir-Hostovsky L
Ivanovska J
Parajón E
Patel R
Wang H
Biouss G
Ivanovski N
Belik J
Pierro A
Montandon G
Gauda EB
Source :: Pediatric research [Pediatr Res] 2023 Sep; Vol. 94 (3), pp. 971-978. Date of Electronic Publication: 2023 Apr 25.
Publication Year :: 2023
Abstract: Background: Leptin augments central CO <subscript>2</subscript> chemosensitivity and stabilizes breathing in adults. Premature infants have unstable breathing and low leptin levels. Leptin receptors are on CO <subscript>2</subscript> 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 <subscript>2</subscript> chemosensitivity. Methods: 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). Results: 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). Conclusions: We describe the developmental profile of the effect of exogenous leptin on CO <subscript>2</subscript> chemosensitivity. Exogenous leptin does not augment central CO <subscript>2</subscript> 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. Impact: Exogenous leptin does not augment CO <subscript>2</subscript> 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 <subscript>2</subscript> 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 <subscript>2</subscript> sensitivity in premature infants. Thus, it is highly unlikely that exogenous leptin would alter this response. (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)