Thyroid hormone deficiency during development is known to cause anatomical defects in the cerebellum that lead to neurological deficits. It has been observed that insufficient thyroid hormone levels also decrease the levels of brain derived Insulin-like growth factor 1 (Igf-1). Given that the deficits caused by low Igf-1 levels are similar to those caused by low thyroid hormone, we designed this study to investigate if the deficits caused in the development of the cerebellum by low thyroid hormone levels may be due to the lack of sufficient Igf-1. We also sought to determine if ectopic over expression of Igf-1 in the brain can ameliorate the defects caused by low thyroid hormone. To do this, we used a double transgenic mouse model that ectopically over expresses Igf-1 in the brain astrocytes, specifically the Bergman glia. To obtain double transgenic mice, we crossed mice that contain the tTA (tetracycline trans activator) transgene driven by the GFAP (glial fibrillary acidic protein) promoter with mice that contain the IGF-1 transgene under the control of the tetracycline response element (pTRE). The double transgenic mice obtained from this cross, over express Igf-1 in brain astrocytes. To induce hypothyroidism, timed pregnant mice were treated with thyroid hormone disrupting chemicals in their drinking water starting at embryonic day 13.5 till pup sacrifice at P12. From each pup, blood and tail was collected, brains were dissected and cryoprotected. Defects in developmental processes in the cerebellum like granule cell proliferation, migration and purkinje cell differentiation were studied using immunohistochemistry. Our results showed no evidence of rescue in the defects caused by hypothyroidism in the presence of ectopic Igf-1 over expression in the brain.
Date of Degree
Master of Science (MS)
Program of Study
Science, Engineering and Technology
Mangedarage, Prathibha. (2023).The Role of Insulin-Like Growth Factor I in the Development of the Cerebellum in Euthyroid and Hypothyroid Mice [Master’s thesis, Minnesota State University, Mankato]. Cornerstone: A Collection of Scholarly and Creative Works for Minnesota State University, Mankato. https://cornerstone.lib.mnsu.edu/etds/1385/
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