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Effects of hypothyroidism induced by perinatal exposure to PTU on rat behavior and synaptic gene expression
Kumiko Kobayashi1, Ryozo Tsuji, Takafumi Yoshioka
1Environmental Health Science Laboratory, Sumitomo Chemical Co. Ltd., 3-1-98 Kasugade-Naka, Konohana-Ku, Osaka 554-8558, Japan. kobayashik7@sc.sumitomo-chem.co.jp
Insights
Perinatal propylthiouracil (PTU) exposure in rats models hypothyroidism, revealing altered gene expression (GAP-43, M1) linked to neurobehavioral defects. This highlights potential molecular markers for early developmental neurotoxicity detection.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Perinatal hypothyroidism in rats, induced by propylthiouracil (PTU), serves as a model for studying neurobehavioral deficits.
- Identifying molecular markers for developmental neurotoxicity is crucial for early detection and intervention.
Purpose of the Study:
- To investigate the effects of a minimal, behavior-altering dose of PTU on specific gene expression in the developing rat brain.
- To assess the relationship between PTU-induced hypothyroidism and changes in genes related to neural network formation and synaptic function.
Main Methods:
- Administration of various PTU doses to pregnant and lactating dams.
- Quantitative RT-PCR analysis of selected gene expression (GAP-43, M1) in the hippocampus and cerebral cortex of offspring.
- Behavioral assessment of PTU-exposed rats, including motor activity and E-maze learning.
Main Results:
- PTU-treated rats exhibited increased motor activity and impaired E-maze learning.
- Expression of GAP-43 and M1 mRNAs was altered in the offspring's brain at doses causing behavioral changes.
- These gene expression changes occurred during critical periods of neuronal network formation.
Conclusions:
- Minimal PTU exposure during development can induce neurobehavioral alterations in rats.
- Changes in GAP-43 and M1 mRNA levels are associated with PTU-induced neurodevelopmental effects.
- These findings suggest GAP-43 and M1 as potential molecular markers for early developmental neurotoxicity.
Abstract:
Hypothyroidism in the rat induced by perinatal exposure to propylthiouracil (PTU) is a useful animal model to study molecular changes underlying neurobehavioral defects associated with this condition. Understanding the developmental alterations in gene expression related to the neurobehavioral dysfunction should help to identify molecular markers for developmental neurotoxicity at an early stage of development. In the present study, we evaluate the effects of PTU on the expression of a set of genes implicated in neural network formation or synaptic function at a minimal dose of PTU causing behavioral alteration. Various doses of PTU were administered to dams from late pregnancy to the lactation period and the expression of selected genes in the hippocampus and the cerebral cortex of offspring was examined by quantitative RT-PCR. Behavioral performance of PTU-treated rats was also assessed. PTU-treated rats showed increased motor activity and impairment of E-maze learning at weaning and after maturation. At doses causing such behavioral alteration, expression of GAP-43 and M1 mRNAs was changed during neuronal network formation, suggesting that levels of these factors during development are important for accurate postnatal development and function.
