Khaled, Mohamed M; (1995) The role of thyroid hormones in the metabolic homeostasis of neuronal and glial cells in culture. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Thyroid hormones (TH) play an important role in early neurogenesis in utero. However, the biochemical and metabolic mechanisms underlying this role has only been scantily investigated, although some reports exist pointing to metabolic dysfunctions in the brain of rat progeny born to hypothyroxinemic dams. In order to further investigate this role we have studied the nature of thyroid hormones influence on amino acid uptake and incorporation into protein as well as [3H]-2-deoxy-D-glucose (2DG) uptake into neural cell culture. Uptake into synaptosomal fractions, prepared from Euthyroid and Hypothyroid adult rats, was also studied. The results show that 2DG uptake into synaptosomes, prepared from euthyroid rats, was not influenced by T3 concentrations between 10-10-10-6 M, while those prepared from hypothyroid rats were responsive and uptake was significantly stimulated by 1-100 nM T3 (by 20-70[percent],). 2DG uptake was inhibited by 1 [mu]M T3 (by 25-70[percent], P[less-than] 0.001) which was abolished by adding 5 mM ATP. However, 2DG uptake into astrocytic culture was totally non responsive to the presence of TH. [3H]-Lysine uptake and incorporation into protein in astrocytic culture was significantly inhibited by the presence of TH. In neuronal culture, uptake and incorporation into acid soluble material was enhanced by 10 nM T3. The uptake was dependent upon protein synthesis, indicating that T3 mediated uptake of [3H]-Lysine in neurons is dependent upon the binding of T3 to the nuclear receptors followed by protein synthesis. Results presented here, together with similar observations made by other researchers, provide evidence that TH in early neurogenesis may have a crucial influence on the metabolic homeostasis of the CNS. In addition, the following postulates will be considered: 1) TH are selective in their influence on different brain cells and metabolic parameters. 2) TH may directly affect the brain, independent of nuclear T3 receptors mediation. 3) TH seems to modulate the optimisation of metabolic homeostatic efficiency rather than drastically altering basic biochemical functions.

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