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Published on: November 20, 2015
Perinatal and chronic hypothyroidism impair behavioural development in male and female rats
N van Wijk1, E Rijntjes, B J M van de Heijning
1Human and Animal Physiology Group, Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands. nick.vanwijk@danone.com
Insights
Hypothyroidism during development impairs neuromotor skills and cognitive function in rats. While chronic hypothyroidism causes lasting hyperactivity and memory deficits, perinatal hypothyroidism
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Thyroid hormone is crucial for normal brain development.
- Hypothyroidism during early life can lead to significant brain alterations.
- The impact of hypothyroidism timing on neurodevelopment requires further investigation.
Purpose of the Study:
- To assess the behavioral effects of perinatal and chronic hypothyroidism during rat development.
- To investigate the reversibility of hypothyroidism-induced neurodevelopmental alterations.
- To compare the effects of hypothyroidism exposure timing on neuromotor, locomotor, and cognitive functions.
Main Methods:
- Induced hypothyroidism in rat dams and offspring using an iodide-poor diet and sodium perchlorate.
- Administered chronic hypothyroidism until postnatal day 71 and perinatal hypothyroidism until weaning.
- Evaluated neuromotor competence (grip, balance beam tests), locomotor activity (open field test), and cognitive function (Morris water maze).
Main Results:
- Both chronic and perinatal hypothyroidism impaired early neuromotor competence.
- Chronic hypothyroidism resulted in hyperactivity and impaired spatial memory.
- Perinatal hypothyroidism impaired spatial memory in female rats, with effects being less pronounced than chronic hypothyroidism.
Conclusions:
- Early hypothyroidism significantly impacts neurodevelopment, affecting neuromotor, locomotor, and cognitive functions.
- The timing and duration of hypothyroidism influence the severity and reversibility of observed effects.
- Findings suggest that developmental timing of thyroid hormone deficiency is critical for functional brain alterations.
Abstract:
A lack of thyroid hormone, i.e. hypothyroidism, during early development results in multiple morphological and functional alterations in the developing brain. In the present study, behavioural effects of perinatal and chronic hypothyroidism were assessed during development in both male and female offspring of hypothyroid rats. To induce hypothyroidism, dams and offspring were fed an iodide-poor diet and drinking water with 0.75% sodium perchlorate; dams starting 2 weeks prior to mating and pups either until the day of killing (chronic hypothyroidism) or only until weaning (perinatal hypothyroidism) to test for reversibility of the effects observed. Neuromotor competence, locomotor activity and cognitive function were monitored in the offspring until postnatal day 71 and were compared with age-matched control rats. Early neuromotor competence, as assessed in the grip test and balance beam test, was impaired by both chronic and perinatal hypothyroidism. The open field test, assessing locomotor activity, revealed hyperactive locomotor behavioural patterns in chronic hypothyroid animals only. The Morris water maze test, used to assess cognitive performance, showed that chronic hypothyroidism affected spatial memory in a negative manner. In contrast, perinatal hypothyroidism was found to impair spatial memory in female rats only. In general, the effects of chronic hypothyroidism on development were more pronounced than the effects of perinatal hypothyroidism, suggesting the early effects of hypothyroidism on functional alterations of the developing brain to be partly reversible and to depend on developmental timing of the deficiency.
