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Published on: July 8, 2025
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.
Background:
Emerging evidence indicates that early adverse experiences result in the maladaptive development of the hypothalamic-pituitary-adrenal (HPA) axis and compromise the developing brain to subsequent neurological insults. Well known that mother-infant interaction plays an important role in early environment stimulation, neonatal isolation (NI) paradigm has been used as an early-life stress model in many relevant studies. Further, the effect of seizure on the developing brain is still not clarified despite more susceptibility to seizures of the developing brain. We had previously demonstrated that NI exacerbates cognitive deficit following early-life seizure. The aim of the current study was to investigate whether NI predisposes the brain to early-life seizure-induced long-term anxiety sequelae.
Methods:
Rats were assigned randomly to the following four groups: (1) normal rearing rats (NR); (2) NI rats that underwent daily separation from their dams from postnatal day 2 (P2) to P9; (3) NR rats suffering lithium-pilocarpine-induced status epilepticus (SE) at P10 (NR+SE); and (4) NI+SE rats. At P60, anxiety-related behavior was evaluated using elevated plus-maze (EPM) test.
Results:
SE induced in isolated rats rather than in NR rats produced a decrease in percentage of time spent in open arms, and all rats experiencing NI displayed reduced number of closed arm entries.
Conclusion:
Repetitive brief NI exacerbates anxiety-related behavior in EPM test following early-life SE.
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