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A Versatile, Behavioral Method to Investigate Thyroid Hormone Effects on Cerebellar Function
Published on: October 6, 2023
PTU-induced hypothyroidism modulates antioxidant defence status in the developing cerebellum
1Department of Biotechnology, Utkal University, Vani Vihar, Bhubaneswar 751004, India. shravanibhanja@rediffmail.com <shravanibhanja@rediffmail.com>
Insights
Thyroid hormone deficiency in developing rats alters cerebellar oxidative stress and antioxidant enzyme activity. This impacts cell proliferation and apoptosis, crucial for neonatal brain development.
Area of Science:
- Neuroscience
- Endocrinology
- Biochemistry
Background:
- Thyroid hormones are critical for normal brain development.
- Hypothyroidism during neonatal development can lead to long-term neurological deficits.
- Oxidative stress plays a role in various neurological disorders.
Purpose of the Study:
- To investigate the impact of 6-n-propylthiouracil (PTU)-induced hypothyroidism on the developing cerebellum.
- To assess changes in oxidative stress markers, antioxidant enzyme expression, cell proliferation, and apoptosis.
Main Methods:
- PTU was administered to induce hypothyroidism in neonatal rats.
- Serum thyroid hormone levels (T3, T4) and TSH were measured.
- Cerebellar oxidative stress (H2O2, lipid peroxidation) and antioxidant enzyme activities (SOD, GPx, catalase) were analyzed.
- Cell proliferation (PCNA) and apoptosis (TUNEL assay) were evaluated.
- Enzyme expression was studied using Western blot and rt-PCR.
Main Results:
- Hypothyroid neonates exhibited decreased T3/T4 and increased TSH.
- Early hypothyroidism (7 days) showed increased cerebellar H2O2, lipid peroxidation, SOD, and GPx, with decreased catalase.
- Later hypothyroidism (30 days) revealed decreased lipid peroxidation, SOD, and GPx, with increased catalase activity and expression.
- Increased cell proliferation (PCNA) was observed at 7 days, followed by a significant drop at 30 days.
- Apoptosis was elevated in the cerebellum of hypothyroid rats.
Conclusions:
- The developing cerebellum's antioxidant defense system is sensitive to thyroid hormone deficiency.
- Altered oxidative stress status in hypothyroidism influences cerebellar cell proliferation and apoptosis.
- These findings highlight the critical role of thyroid hormones in regulating neonatal cerebellar development and oxidative balance.
Abstract:
The objective of the present study was to evaluate the effect of 6-n-propylthiouracil (PTU)-induced hypothyroidism on oxidative stress parameters, expression of antioxidant defence enzymes, cell proliferation and apoptosis in the developing cerebellum. PTU challenged neonates showed significant decrease in serum T(3) and T(4) levels and marked increase in TSH levels. Significantly elevated levels of cerebellar H(2)O(2) and lipid peroxidation were observed in 7 days old hypothyroid rats, along with increased activities of superoxide dismutase and glutathione peroxidase and decline in catalase activity. In 30 days old hypothyroid rats, a significant decline in cerebellar lipid peroxidation, superoxide dismutase and glutathione peroxidase activity and expression was observed along with an up-regulation in catalase activity and expression. Expression of antioxidant enzymes was studied by Western blot and semi-quantitative rt-PCR. A distinct increase in cell proliferation as indicated by proliferating cell nuclear antigen (PCNA) immunoreactivity was observed in the internal granular layer of cerebellum of 7 days old hypothyroid rats and significant drop in PCNA positive cells in the cerebellar molecular layer and internal granular layer of 30 days old PTU treated rats as compared to controls. In situ end labeling by TUNEL assay showed increased apoptosis in cerebellum of hypothyroid rats in comparison to controls. These results suggest that the antioxidant defence system of the developing cerebellum is sensitive to thyroid hormone deficiency and consequent alterations in oxidative stress status may play a role in regulation of cell proliferation of the cerebellum during neonatal brain development.
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