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A Versatile, Behavioral Method to Investigate Thyroid Hormone Effects on Cerebellar Function
Published on: October 6, 2023
Hypothyroidism alters mitochondrial morphology and induces release of apoptogenic proteins during rat cerebellar
R Singh1, Geeta Upadhyay, M M Godbole
1Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, India.
Abstract:
Thyroid hormone (TH) deficiency leads to extensive apoptosis during cerebellar development, but the mechanism still remains unclear. Different signals also converge on mitochondria during apoptosis to induce the release of apoptogenic proteins that activate proteolytic cascade through specific enzymes called caspases. Here we studied the effect of hypothyroidism on alterations in mitochondrial structure and translocation of apoptogenic molecules during rat cerebellar development. Structural analysis of mitochondria was studied by electron microscopy. The translocation of apoptogenic molecules was analyzed by Western blotting. TH deficiency led to vacuolization, enlargement and decrease in the number of cristae. The majority of the proapoptotic molecule, Bax, was localized in mitochondria under hypothyroid conditions whereas a limited presence of Bax was detected in the euthyroid state. Translocation of cytochrome c, apoptosis-inducing factor (AIF) and second mitochondrial-derived activator of caspases (SMAC) from mitochondria to cytosol was detected primarily in early developmental stages in the hypothyroid condition. These experimental results demonstrate that TH maintains mitochondrial architecture and inhibits the release of apoptogenic molecules to prevent excess apoptosis during cerebellar development.
Insights
Thyroid hormone (TH) deficiency causes mitochondrial damage and releases apoptosis-inducing molecules in developing rat cerebellums. This research clarifies how TH deficiency leads to excessive cell death during development.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Thyroid hormone (TH) is crucial for cerebellar development.
- TH deficiency is linked to increased apoptosis, but mechanisms are unclear.
- Mitochondria play a key role in apoptosis by releasing specific proteins.
Purpose of the Study:
- To investigate the impact of hypothyroidism on mitochondrial structure and function during rat cerebellar development.
- To analyze the translocation of apoptogenic molecules in hypothyroid rat cerebellums.
Main Methods:
- Mitochondrial structure was analyzed using electron microscopy.
- The translocation of apoptogenic molecules (Bax, cytochrome c, AIF, SMAC) was assessed via Western blotting.
Main Results:
- Hypothyroidism induced mitochondrial vacuolization, enlargement, and reduced cristae.
- The proapoptotic molecule Bax predominantly localized to mitochondria in hypothyroid rats.
- Apoptogenic molecules (cytochrome c, AIF, SMAC) translocated from mitochondria to the cytosol during early development in hypothyroid conditions.
Conclusions:
- Thyroid hormone is essential for maintaining normal mitochondrial architecture in the developing cerebellum.
- TH deficiency promotes the release of mitochondrial apoptogenic factors, contributing to excessive apoptosis.
- These findings elucidate a key mechanism by which TH regulates cerebellar development and prevents cell death.
