Abstract

Hypothyroidism has been known to result in numerous neuroanatomical defects in the developing brain. To investigate further into the mechanism in which these defects are obtained, local brain insulin-like growth factor 1 (Igf1) was investigated in relation to the hypothyroid brain. There are many similarities between hypothyroidism and the Igf1 deficient brain. Additionally, TH (thyroid hormone) is known to interact with Igf1. Therefore, the purpose of this study was to investigate the effect of induced congenital hypothyroidism on the temporal expression of Igf1-positive cells in the brain. To investigate the relationship between TH and Igf1 in the brain, we inhibited TH production in C57BL6J mice by the administration of 1% KClO4 and 0.05% MMI in drinking water from 14 (embryonic day 14) to P21 (postnatal day 21). Control and hypothyroid mice were sacrificed at select developmental time points (P7, P14, P21, P42). Serum was collected to measure Igf1 and T4 (thyroxine) by ELISA. Brain tissues were collected and cryosectioned to obtain the frontal motor cortex, hippocampus, and cerebellum, in which in situ hybridization was performed. From the in situ hybridization, Igf1-positive cells and relative Igf1 mRNA levels were analyzed. Serum T4 and Igf1 data was consistent with previous literature that indicated low TH decreases Igf1 in the serum. Additionally, serum TH and serum Igf1 are positively correlated and both peak in unison. Furthermore, also consistent with previous findings, low TH resulted in a decrease of Igf1 mRNA in the brain. A significant reduction of Igf1-positive cells was evident in the frontal motor cortex of hypothyroid treated animals, but no other region, demonstrating region specific expression of Igf1-positive cells. Additionally, we showed that the previously reported reduction of Igf1 mRNA in the hypothyroid brain was not due to a decrease in Igf1 mRNA synthesis in the cortex, hippocampus, or cerebellum, but potentially rather a total loss of Igf1-positive cells, like that of the cortex.

Advisor

David Sharlin

First Committee Member

Rachel Cohen

Second Committee Member

Michael Bentley

Date of Degree

2015

Language

english

Document Type

Thesis

Degree

Master of Science (MS)

Department

Biological Sciences

College

Science, Engineering and Technology

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

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