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Neurodevelopment milestone abnormalities in rats exposed to stress in early life
A R Mesquita1, J M Pêgo, T Summavielle
1Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
Insights
Postnatal stress in infant rats impairs neurodevelopment and neurological reflexes, particularly in males for some reflexes. This stress impacts monoamine levels in the brain stem, suggesting a link to future behavioral issues.
Area of Science:
- Neuroscience
- Developmental Psychology
- Animal Behavior
Background:
- Maternal separation and stress can impact corticosteroid levels and have long-term effects on psychopathology.
- Understanding the neurodevelopmental consequences of early life stress is crucial for identifying potential interventions.
Purpose of the Study:
- To systematically assess neurodevelopmental milestones in infant rats subjected to maternal separation.
- To investigate the impact of postnatal stress on neurological reflexes and monoamine levels in the brain stem.
- To explore potential gender differences in the neurodevelopmental effects of early life stress.
Main Methods:
- Infant rats were deprived of maternal contact for 6 hours daily between postnatal days 2-15.
- Neurodevelopmental milestones, physical growth, and neurological reflexes were assessed up to postnatal day 21.
- Monoamine levels and turnover (including 5-HT, 5-HIAA, and DOPAC) were measured in specific brain stem regions.
Main Results:
- Maternal separation led to delayed acquisition of postural, air righting, and surface righting reflexes, particularly in males.
- Negative geotaxis was impaired in females but not males.
- Reduced serotonin (5-HT) levels and increased 5-HT turnover were observed in the vestibular region; 5-HT turnover increased in the raphe nuclei.
- Increased DOPAC levels were found in the ventral tegmental area (VTA) of stressed females.
Conclusions:
- Postnatal stress significantly delays neurological maturation and alters monoamine levels in the brain stem.
- These neurochemical changes may underlie the observed neurological deficits and contribute to behavioral abnormalities later in life.
- Gender-specific effects highlight the complex interplay between early stress, neurodevelopment, and sex hormones.
Abstract:
Manipulation of the corticosteroid milieu by interfering with the mother-newborn relationship has received much attention because of its potential bearing on psychopathology later in life. In the present study, infant rats that were deprived of maternal contact between the 2nd and the 15th postnatal days (MS2-15) for 6 h/day were subjected to a systematic assessment of neurodevelopmental milestones between postnatal days 2 and 21. The analyses included measurements of physical growth and maturation and evaluation of neurological reflexes. Although some somatic milestones (e.g. eye opening) were anticipated, MS2-15 animals showed retardation in the acquisition of postural reflex, air righting and surface righting reflexes, and in the wire suspension test; the latter two abnormalities were only found in males. A gender effect was also observed in negative geotaxis, with retardation being observed in females but not males. To better understand the delay of neurological maturation in MS2-15 rats, we determined the levels of various monoamines in different regions of the brain stem, including the vestibular area, the substantia nigra, ventral tegmental area and dorsal raphe nuclei. In the vestibular region of MS2-15 rats the levels of 5-HT were reduced, while 5-HT turnover was increased. There was also a significant increase of the 5-HT turnover in MS2-15 animals in the raphe nuclei, mainly due to increased 5-hydroxyindoleacetic acid (5-HIAA) levels, and an increase of 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the ventral tegmental area (VTA) of stressed females. No significant differences were found in the immunohistochemical sections for tyrosine and tryptophan hydroxylase in these regions of the brain stem. In conclusion, the present results show that postnatal stress induces signs of neurological pathology that may contribute to the genesis of behavioral abnormalities later in life.
