Degree Type

Dissertation

Date of Award

1985

Degree Name

Doctor of Philosophy

Department

Theses & dissertations (Interdisciplinary)

Major

Molecular, Cellular, and Developmental Biology

Abstract

Gold thioglucose (GTG) lesion formation in the mouse ventromedial hypothalamus (VMH) has sparked controversy over the last 15 years. Specifically, the mechanism of GTG action in the VMH has been disputed. The ultrastructural studies undertaken in this project, utilizing intraperitoneal (IP) subnecrotic (100 mg/kg) or necrotic (300 or 800 mg/kg) doses of GTG to produce microlesions and macrolesions, respectively, have demonstrated GTG damaged VMH nervous tissue prior to any vascular destruction. Thus, the concept that GTG is a nervpus tissue toxin as opposed to a vascular toxin in mice has been substantiated;Stressors, which are known to induce hormonal alterations, abolished GTG lesion formation in the mouse VMH. Consistent with previous reports in the literature, prevention of GTG-induced damage in the VMH of stressed mice is apparently caused by an elevation of glucocorticoid levels due to the stress;Loading mice with tyrosine, the precursor for catecholamines, had no effect on GTG lesion formation. However, administration of alphamethylparatyrine, an inhibitor of catecholamine synthesis, enhanced VMH lesion size from a standard GTG challenge. While tyrosine loading had no effect on GTG lesion formation, tryptophan loading produced significantly smaller GTG-induced lesions in the VMG compared controls. This phenomenon was only observed in mice injected with tryptophan IP on a long term basis, and may be associated with tryptophan hydroxylase activity and/or serotonin turnover;The VMH exhibits a preference for glucose as a metabolic substate. Inhibitors of glucose oxidation and/or transport only reduced in vitro VMH glucose utilization when present in extremely large concentrations; some reputed glucose inhibitory compounds had no effect on VMH glucose oxidation. Furthermore, the glucoreceptor antagonist and diabetogenic agent, alloxan, depressed glucose oxidation in the VMH significantly. With respect to GTG lesion formation, phlorizin (a glucose transport inhibitor) abolished GTG lesion formation in the VMH, however digitoxose (a reputed glucoreceptor competitor) had no effect on GTG-induced necrosis in the VMH.

DOI

https://doi.org/10.31274/rtd-180813-5559

Publisher

Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/

Copyright Owner

Danley Fritz Brown

Language

en

Proquest ID

AAI8514377

File Format

application/pdf

File Size

230 pages

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