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Maternal hypothyroxinemia and brain development: II. Biochemical, metabolic and behavioural correlates
A K Sinha1, M R Pickard, M J Hubank
1Department of Molecular Endocrinology, University College and Middlesex School of Medicine, London, United Kingdom.
Insights
Maternal hypothyroxinemia during pregnancy negatively impacts progeny brain development, affecting protein distribution, glycoproteins, and enzyme activity. These changes correlate with altered behavior in young and adult rats.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Maternal thyroid hormone availability is crucial for fetal brain development.
- Hypothyroxinemia, or low thyroxine levels, during pregnancy can have lasting effects.
Purpose of the Study:
- To investigate the impact of maternal hypothyroxinemia on brain development in rat progeny.
- To examine changes in protein distribution, glycoproteins, enzyme activity, and behavior.
Main Methods:
- A rat model was used to induce maternal hypothyroxinemia throughout pregnancy.
- Brain tissue analysis included protein concentration, glycoprotein isolation (concanavalin A-affinity chromatography, gel electrophoresis), enzyme assays, and cerebroside sulphate content.
- Behavioral assessments were conducted on progeny.
Main Results:
- Maternal hypothyroxinemia altered subcellular protein distribution and specific glycoprotein species in developing brains.
- Key enzymes like calcineurin and lysosomal enzymes were compromised in young progeny.
- Adult progeny showed reduced myelin galactolipid (cerebroside sulphate) and altered acetylcholine metabolism, linked to behavioral changes.
Conclusions:
- Maternal thyroxine is critical for normal fetal brain development and function.
- Hypothyroxinemia can lead to persistent neurodevelopmental deficits and functional impairments.
Abstract:
Using a rat model, we have investigated the influence of maternal hypothyroxinemia throughout pregnancy on brain development in young and adult progeny. Although no consistent change was observed in whole brain total protein concentration, the subcellular distribution of protein was adversely affected. Isolation of glycoprotein from developing brain by concanavalin A-affinity chromatography and subsequent resolution by gel electrophoresis revealed the selective compromise of particular glycoprotein species. Furthermore, both control and experimental progeny expressed unique glycoprotein species which either persisted over the period studied or were transient. Calcineurin, a regulator of neurite elongation, was compromised in young progeny, as were a number of lysosomal enzymes (beta-D-glucosidase and aryl sulphatase). In adult progeny, the content of cerebroside sulphate (a major myelin galactolipid) was reduced in midbrain and paleocortex, and brain region-specific compromise was observed for acetylcholine metabolic enzymes. These changes were associated with alterations in behavioural output. We conclude that the availability of maternal thyroxine to the fetus may be a critical determinant for normal brain development and function.