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Long-lasting effects of elevated neonatal leptin on rat hippocampal function, synaptic proteins and NMDA receptor

Claire-Dominique Walker1, Hong Long, Sylvain Williams

  • 1Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal, Quebec, Canada. waldom@douglas.mcgill.ca

Journal of Neuroscience Research
|January 25, 2007
PubMed

Insights

High neonatal leptin levels impact brain development, altering hippocampal function and synaptic protein production. These changes affect neurotransmitter release and synaptic plasticity, with lasting effects on brain development.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Endocrinology

Background:

  • Neonatal rodents exhibit high leptin levels, suggesting roles beyond energy balance.
  • Leptin's influence on brain development, particularly hippocampal function, is under investigation.
  • Understanding leptin's neonatal effects is crucial for comprehending long-term neurological outcomes.

Purpose of the Study:

  • To investigate the hypothesis that high neonatal leptin levels modify hippocampal function and synaptic protein production.
  • To determine the long-term consequences of neonatal leptin exposure on long-term potentiation (LTP) in adulthood.
  • To elucidate the effects of chronic leptin administration on NMDA receptor subunits and synaptic proteins in the developing hippocampus.

Main Methods:

  • Acute leptin treatment in neonatal rats (postnatal day 10) to assess hippocampal leptin receptor (ObR) activation via phospho-ERK1/2 and phosphoSTAT3.
  • Chronic leptin administration (3 mg/kg BW, PND 2-14) to evaluate effects on hippocampal synaptic proteins and LTP.
  • Analysis of NMDA receptor subunits (NR1, NR2A, NR2B), synapsin2A, synaptophysin, and SNAP-25 expression.
  • Assessment of long-term potentiation (LTP) in preweaning and adult rats.

Main Results:

  • Acute leptin activated hippocampal ObR in CA1 and DG regions of PND 10 neonates.
  • Chronic neonatal leptin increased hippocampal NR1 and decreased NR2B expression in both PND 10 and PND 70 rats.
  • Elevated synapsin2A and synaptophysin were observed on PND 10, indicating increased neurotransmitter release.
  • Neonatal leptin reduced LTP in preweaning rats, but this effect did not persist into adulthood.
  • SNAP-25 expression was increased in adults following neonatal leptin treatment.

Conclusions:

  • Neonatal leptin exposure significantly impacts hippocampal development and function.
  • Leptin's effects include alterations in NMDA receptor subunits and synaptic protein expression.
  • Neonatal leptin exposure may enhance NMDA-dependent functions beyond LTP and influence synaptogenesis and neurotransmitter release.

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