Neonatal leptin administration alters regional brain volumes and blocks neonatal growth restriction-induced behavioral and cardiovascular dysfunction in male mice.
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.
Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
Gwen E
GE
Erkonen
Gregory M
GM
Hermann
Rachel L
RL
Miller
Daniel L
DL
Thedens
Peg C
PC
Nopoulos
John A
JA
Wemmie
Robert D
RD
Roghair
D000367:Age Factors; D000375:Aging; D000679:Amygdala / Q000187:drug effects* / Q000254:growth & development; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D003213:Conditioning, Psychological / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D005260:Female; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D020738:Leptin / Q000008:administration & dosage* / Q000097:blood; D008098:Litter Size; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009929:Organ Size; D010641:Phenotype; D012737:Sex Factors
D020738:Leptin
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