Neonatal leptin administration alters regional brain volumes and blocks neonatal growth restriction-induced behavioral and cardiovascular dysfunction in male mice

Gwen E Erkonen; Gregory M Hermann; Rachel L Miller; Daniel L Thedens; Peg C Nopoulos; John A Wemmie; Robert D Roghair

doi:10.1203/PDR.0b013e3182110c7d

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Neonatal leptin administration alters regional brain volumes and blocks neonatal growth restriction-induced behavioral and cardiovascular dysfunction in male mice

Journal article

Open access

Peer reviewed

Neonatal leptin administration alters regional brain volumes and blocks neonatal growth restriction-induced behavioral and cardiovascular dysfunction in male mice

Gwen E Erkonen, Gregory M Hermann, Rachel L Miller, Daniel L Thedens, Peg C Nopoulos, John A Wemmie and Robert D Roghair

Pediatric research, Vol.69(5 Pt 1), pp.406-412

05/2011

DOI: 10.1203/PDR.0b013e3182110c7d

PMCID: PMC3095021

PMID: 21258265

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Abstract

Premature delivery is often complicated by neonatal growth restriction (GR) and neurodevelopmental impairment. Because global overnutrition increases the risk of adult metabolic syndrome, we sought a targeted intervention. Premature delivery and perinatal GR decrease circulating levels of the neurotrophic hormone leptin. We hypothesized that leptin supplementation would normalize the outcomes of mice with incipient neonatal GR. Pups were fostered into litters of 6 or 12 to elicit divergent growth patterns. Pups in each litter received injections of saline or leptin from d 4 to 14. At 4 mo, mice underwent tail cuff blood pressure measurement, behavioral testing, and MRI. Mice fostered in litters of 12 had decreased weanling weights and leptin levels. Neonatal leptin administration normalized plasma leptin levels without influencing neonatal growth. Leptin replacement also normalized the hypertension, stress-linked immobility, conditioned fear, and amygdala enlargement seen in neonatal growth restricted male mice. In control males, neonatal leptin administration led to hypothalamic enlargement, without overt neurocardiovascular alterations. Female mice were less susceptible to the effects of neonatal GR or leptin supplementation. In conclusion, the effects of neonatal leptin administration are modulated by concurrent growth and gender. In growth restricted male mice, physiologic leptin replacement improves adult neurocardiovascular outcomes.

Aging

Magnetic Resonance Imaging

Phenotype

Amygdala - drug effects

Age Factors

Body Weight - drug effects

Fear - drug effects

Motor Activity - drug effects

Hypertension - drug therapy

Male

Cardiovascular System - physiopathology

Leptin - blood

Behavior, Animal - drug effects

Female

Leptin - administration & dosage

Blood Pressure - drug effects

Animals, Newborn

Litter Size

Conditioning (Psychology) - drug effects

Mice, Inbred C57BL

Injections, Intraperitoneal

Organ Size

Cardiovascular System - drug effects

Hypertension - physiopathology

Animals

Sex Factors

Amygdala - growth & development

Mice

Details

Title: Subtitle: Neonatal leptin administration alters regional brain volumes and blocks neonatal growth restriction-induced behavioral and cardiovascular dysfunction in male mice
Creators: Gwen E Erkonen - Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA
Gregory M Hermann
Rachel L Miller
Daniel L Thedens
Peg C Nopoulos
John A Wemmie
Robert D Roghair
Resource Type: Journal article
Publication Details: Pediatric research, Vol.69(5 Pt 1), pp.406-412
DOI: 10.1203/PDR.0b013e3182110c7d
PMID: 21258265
PMCID: PMC3095021
NLM abbreviation: Pediatr Res
ISSN: 0031-3998
eISSN: 1530-0447
Publisher: United States
Grant note: R01 HL102659-01A1 / NHLBI NIH HHS R01 HL102659 / NHLBI NIH HHS HL102659 / NHLBI NIH HHS R01 HL102659-02 / NHLBI NIH HHS
Language: English
Date published: 05/2011
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Neurology; Radiology; Electrical and Computer Engineering; Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neonatology; Neurosurgery
Record Identifier: 9984003972302771

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