Data of histochemical studies suggest that THs exert significant influences on myelination and the process of neuron degenerations leading to deficit in brain development. Results of IHC in this study are not fully matched to gene transcription results. It indicates that gene transcriptions may not be synonymous with gene translation. The ratio of RNA transcripts to proteins may differ among genes. It suggested that the transcriptional and morphological studies are supplementary to each other. / In this study, hypothyroidism was induced by different regimens. They are 0.05% methimazole (MMI), 0.02% MMI plus 1% NaC1O4, and 0.1% propyl-thiouracil in drinking water of mother rats from day 16 of their pregnancies, postnatal day 1 or day 4 to day 24. The replacement therapy was done by giving either a single s.c. injection of 300 nM T4 18 hrs before sacrifice on postnatal day 16, or by giving s.c. daily injections of 1.5 ng T3 plus 9 ng T4 per gram body weight from postnatal day 11 to 15. Olfactory bulb (OB), hippocampus (H) and cerebellum (CM) and in some cases also cerebral cortex (CX) were studied. The axon guidance molecules and their related genes, Galpha proteins, RGSs and small GTPases mRNA levels were examined with Real-Time quantitative RT-PCR. Special staining on sagittal frozen brain sections with histochemical and immunohistochemical (IHC) techniques were also studied. / It is well established that neonatal hypothyroidism causes defective development of the brain. As signals for synaptogenesis, growth factors and their receptors regulate the gene expression of the growth cone proteins and axon guidance molecules, and control the differentiation of neurons during brain development. Galpha proteins are signal transducers and regulators of G protein signaling (RGS) proteins are recently identified family of proteins that dampen G protein-coupled receptor-mediated signaling by accelerating the intrinsic GTPase activity of Galpha proteins. They play important roles in determining the intensity and specificity of signaling pathways in brain and their adaptations to synaptic activities. / The transcript abundance of some genes, such as Galphai1, Galphai2, Galphaol, Galphas, RGS 2, - 4, -5, -7, -8, -12, -16, -17, Mfn2, TRalpha1, TRbeta 1, Rheb, Rhes, Dexras1, Plexin1, Citron-Kinase, GAP-43, CRMP1, CRMP3, CRMP4 and CRMP5 in CM; Galpha12, Galphai3, G alphaol, Galphaolf, Galphaq, RGS 5, - 7, -8, -16, cdc42, Rhes, TC10, Dexras1, Citron-Kinase, TRalpha1, CRMP2, Wnt7A, Sema3A and GAP43 in OB and Galpha12, Galphai1 , Galphai2, Galphao2, RGS 5, -8, - 16, Mfn1, Mfn2, TRalpha1, Rhes, TC10, Dexras1, Citron-Kinase, GAP-43, CRMPI1, CRMP4, CRMP5 and Gda in H; TRalpha1, CRMP1, CRMP4, CRMP5, Plexin1, Plexin2, Gda and GAP-43 in CX are significantly altered in the neonatal hypothyroid rats. Of note, the mRNA levels of several genes were normalized by TH replacement therapy. Close correlations were found among various Galpha proteins, RGS genes, small GTPases and some axon guidance molecules in a brain- region- specific manner. Our results indicate certain direct or indirect transcriptional effects of the THs on the expression of brain development-related genes and these effects are probably under both temporal and spatial regulations during brain development. / by Yan, Ran. / "January 2007." / Advisers: Michael S. C. Tam; Chun Cheung Wong. / Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5776. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 199-238). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_343824 |
| Date | January 2007 |
| Contributors | Yan, Ran., Chinese University of Hong Kong Graduate School. Division of Physiology. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, theses |
| Format | electronic resource, 1 online resource (xxiii, 239 p. : ill.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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