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Prenatal thyroxine treatment disparately affects peripheral and amygdala thyroid hormone levels
Pradeep K Shukla1, Laura J Sittig, Brian M Andrus
1Department of Psychiatry and Behavioral Sciences, The Asher Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Psychoneuroendocrinology
|December 17, 2009
Summary
Prenatal thyroxine (T4) treatment in Wistar Kyoto rats did not alter depressive behaviors but increased anxiety. This suggests T4 influences adult anxiety via amygdalar gene expression changes.
Area of Science:
- Neuroendocrinology
- Behavioral Neuroscience
- Developmental Biology
Background:
- Prenatal hypothyroidism is linked to adult behavioral issues.
- Wistar Kyoto (WKY) rats naturally exhibit hypothyroidism and heightened anxiety/depressive behaviors.
- WKY rats serve as a model to study developmental hypothyroidism's impact on behavior.
Purpose of the Study:
- To investigate the effects of maternal thyroxine (T4) treatment on thyroid hormone regulation and adult behavior in WKY rat offspring.
- To explore the molecular mechanisms underlying behavioral changes induced by prenatal T4 administration.
Main Methods:
- Pregnant WKY dams received T4 treatment during gestation.
- Adult male offspring were assessed for depressive and anxiety-like behaviors.
- Thyroid hormone levels, and protein/mRNA expression of key regulatory molecules (MCT-8, Dio3, GR, prepro-TRH, CRH) were measured in plasma, hippocampus, and amygdala.
Main Results:
- Prenatal T4 did not affect depressive behavior but increased anxiety-like behavior and decreased plasma thyroid hormone levels.
- In the hippocampus, T4 treatment upregulated Dio3 and MCT-8 protein.
- The amygdala showed increased free T4, MCT-8, GR, prepro-TRH, and CRH mRNA levels.
Conclusions:
- Maternal T4 administration during gestation differentially programs peripheral and amygdalar thyroid hormone levels in WKY offspring.
- Upregulation of anxiety-related genes in the amygdala following prenatal T4 may explain the observed increase in anxiety-like behavior.
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