Neonatal isolation enhances anxiety-like behavior following early-life seizure in rats

Ming-Chi Lai1, San-Nan Yang, Li-Tung Huang

  • 1The Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Insights

Neonatal isolation (NI) in rats worsens anxiety behaviors after early-life seizures. This early-life stress model highlights long-term neurological consequences and impacts the developing brain.

Area of Science:

  • Neuroscience
  • Developmental Psychology
  • Stress Research

Background:

  • Early adverse experiences, such as neonatal isolation (NI), can maladaptively alter the hypothalamic-pituitary-adrenal (HPA) axis and compromise brain development.
  • Neonatal isolation is a recognized model for early-life stress, impacting mother-infant interaction and early environmental stimulation.
  • The developing brain's susceptibility to seizures and the long-term effects of early-life seizures remain incompletely understood.

Purpose of the Study:

  • To investigate if neonatal isolation (NI) predisposes the brain to long-term anxiety sequelae following early-life seizures.
  • To examine the combined effects of early-life stress and seizures on anxiety-related behaviors.
  • To build upon previous findings showing NI exacerbates cognitive deficits after early-life seizures.

Main Methods:

  • Rats were divided into four groups: normal rearing (NR), neonatal isolation (NI), NR with lithium-pilocarpine-induced status epilepticus (SE) at postnatal day 10 (NR+SE), and NI+SE.
  • Neonatal isolation involved daily separation from dams from postnatal day 2 to P9.
  • Anxiety-related behavior was assessed at postnatal day 60 using the elevated plus-maze (EPM) test.

Main Results:

  • Status epilepticus (SE) induced in isolated rats, but not in normal-reared rats, led to a reduced percentage of time spent in the open arms of the elevated plus-maze.
  • All rats exposed to neonatal isolation (NI) showed a decreased number of entries into the closed arms.
  • These results indicate that early-life isolation exacerbates anxiety-like behaviors following early-life seizures.

Conclusions:

  • Repetitive brief neonatal isolation (NI) significantly exacerbates anxiety-related behaviors in the elevated plus-maze test after early-life status epilepticus (SE).
  • Early-life stress, modeled by NI, can have lasting detrimental effects on emotional regulation and brain function following neurological insults.
  • The findings underscore the critical role of early environmental factors in modulating the brain's vulnerability to subsequent stressors and neurological events.
Abstract

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