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Published on: December 14, 2014
Sex differences in heart rate variability during sleep following prenatal nicotine exposure in rat pups
Carie R Boychuk1, David D Fuller, Linda F Hayward
1University of Florida, College of Veterinary Medicine, Department of Physiological Sciences, Gainesville, FL 32610, United States.
Insights
Prenatal nicotine exposure (PNE) in male rat pups alters heart rate regulation during sleep, potentially due to reduced orexin system activity. These sex-specific effects resolve by P16.
Area of Science:
- Neuroscience
- Developmental Biology
- Cardiovascular Physiology
Background:
- Prenatal nicotine exposure (PNE) is a significant concern affecting neurodevelopment.
- Autonomic nervous system regulation of heart rate (HR) during sleep is crucial for development.
- Sex-specific effects of developmental exposures are increasingly recognized.
Purpose of the Study:
- To investigate the influence of PNE and sex on heart rate (HR) regulation during sleep and wakefulness in developing rat pups.
- To explore the relationship between PNE, autonomic control, and the orexin system.
- To determine the developmental trajectory of these effects.
Main Methods:
- Chronic instrumentation of rat pups for heart rate (HR) and heart rate variability (HRV) monitoring.
- Assessment of sleep-wake states (NREM sleep, wakefulness).
- Analysis of hypothalamic prepro-orexin mRNA expression.
Main Results:
- P13 PNE male pups showed increased NREM sleep time and a greater HR drop during sleep onset, linked to reduced sympathovagal balance (LF/HF ratio).
- P13 PNE female pups exhibited decreased parasympathetic drive (HF power) independent of sleep state.
- These PNE-induced effects on HR and HRV were resolved by postnatal day 16 (P16) in both sexes.
- PNE significantly reduced hypothalamic prepro-orexin mRNA levels, with the lowest levels observed in PNE males.
Conclusions:
- PNE induces transient, sex-dependent alterations in sleep-related autonomic HR regulation during early postnatal development.
- These changes may be mediated by epigenetic modifications within the orexin system.
- The findings highlight the vulnerability of early development to environmental exposures like nicotine.
Abstract:
The influence of both prenatal nicotine exposure (PNE; 6 mg/kg/day) and sex on heart rate (HR) regulation during sleep versus wakefulness was evaluated in 13, 16 and 26 day old rat pups. Pups were chronically instrumented at least 24 h before testing. On postnatal day 13 (P13), PNE males spent significantly more time in NREM sleep and demonstrated a greater drop in HR when transitioning from quiet wake to sleep compared to age and sex matched controls (-14±5 bpm versus -1±3 bpm, respectively). Heart rate variability (HRV) analysis indicated that this state-dependent drop in HR was primarily associated with a greater reduction in sympathovagal balance (LF/HF ratio) in PNE males compared to controls. No parallel changes in indices of parasympathetic drive (HF power) were identified. In contrast, no significant effect of PNE on HR during sleep versus wakefulness was identified in P13 females. However, independent of state, a significant decrease in HF power was identified in P13 PNE females compared to controls. At P16, state-dependent differences in HR or HRV between PNE and sex-matched control pups were resolved. Additionally, at P26 no significant effect of PNE on state-dependent changes in HR or HRV was identified in either sex. Analysis of the hypothalamic peptide orexin identified that PNE induced approximately a 50% reduction in hypothalamic prepro-orexin mRNA and total mRNA was lowest in PNE males. These findings suggest that PNE induces sex dependent changes in sleep related autonomic regulation of HR during early postnatal development and these changes may be related to epigenetic alterations in the orexin system.
