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Growth restriction, leptin, and the programming of adult behavior in mice
Journal article   Peer reviewed

Growth restriction, leptin, and the programming of adult behavior in mice

Lauritz R Meyer, Vivian Zhu, Alise Miller and Robert D Roghair
Behavioural brain research, Vol.275, pp.131-135
12/15/2014
DOI: 10.1016/j.bbr.2014.08.054
PMCID: PMC4252372
PMID: 25196633
url
http://doi.org/10.1016/j.bbr.2014.08.054View
Open Access

Abstract

Prematurity and neonatal growth restriction (GR) are risk factors for autism and attention deficit hyperactivity disorder (ADHD). Leptin production is suppressed during periods of undernutrition, and we have shown that isolated neonatal leptin deficiency leads to adult hyperactivity while neonatal leptin supplementation normalizes the brain morphology of GR mice. We hypothesized that neonatal leptin would prevent the development of GR-associated behavioral abnormalities. From postnatal day 4-14, C57BL/6 mice were randomized to daily injections of saline or leptin (80ng/g), and GR was identified by a weanling weight below the tenth percentile. The behavioral phenotypes of GR and control mice were assessed beginning at 4 months. Within the tripartite chamber, GR mice had significantly impaired social interaction. Baseline escape times from the Barnes maze were faster for GR mice (65+/-6s vs 87+/-7s for controls, p<0.05), but GR mice exhibited regression in their escape times on days 2 and 3 (56% regressed vs 22% of control saline mice, p<0.05). Compared to controls, GR mice entered the open arms of the elevated plus maze more often and stayed there longer (72+/-10s vs 36+/-5s, p<0.01). Neonatal leptin supplementation normalized the behavior of GR mice across all behavioral assays. In conclusion, GR alters the social interactions, learning and activity of mice, and supplementation with the neurotrophic hormone leptin mitigates these effects. We speculate neonatal leptin deficiency may contribute to the adverse neurodevelopmental outcomes associated with postnatal growth restriction, and postnatal leptin therapy may be protective.
 Animals, Newborn Drug Administration Schedule Developmental Disabilities - metabolism Developmental Disabilities - etiology Leptin - metabolism Mice, Inbred C57BL Developmental Disabilities - prevention & control Behavior, Animal - physiology Animals Analysis of Variance Spatial Learning Fear - psychology Restraint, Physical - adverse effects Behavior, Animal - drug effects Leptin - administration & dosage Mice Developmental Disabilities - complications Interpersonal Relations Anxiety - etiology Frontal Lobe - pathology Disease Models, Animal

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