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Genetic hypothyroid mice: normal cerebellar morphology but altered glycerol-3-phosphate dehydrogenase in Bergmann glia 总被引:2,自引:0,他引:2
The present study was undertaken to investigate the effects of thyroid deficiency on cerebellar development with mouse endocrine genetic models. Four types of mutant mice, the growth hormone- and thyroid hormone-deficient Snell dwarf mouse (dw/dw), the growth hormone-deficient little mouse (lit/lit), the primary hypothyroid mouse (hyt/hyt), and the congenital genital goiter mouse (cog/cog) were analyzed for expression of the glial enzyme marker glycerol-3-phosphate dehydrogenase (GPDH) and several other marker proteins. GPDH expression, as determined by enzyme activity and Northern blot analysis, was reduced by about 50% in the cerebellum and brainstem of the three hypothyroid mutant mice. No reduced expression was found in any region of the brain of the growth hormone-deficient lit/lit mutant. Visualization of GPDH by immunohistology showed that the immunoreactive enzyme was strikingly reduced in the Bergmann glial cells of dw/dw, hyt/hyt, and cog/cog mutant mice, particularly in the radial glial processes. To evaluate the specificity of the effect on GPDH expression, we also examined the expression of the glial cell-specific S-100 protein by immunohistology. In all mutant cerebella, both the intensity and pattern of staining of the Bergmann glial cells were indistinguishable from that of normal controls, suggesting that the Bergmann glial cells are morphologically normal in the hypothyroid mice. The morphology of the Purkinje cell neurons was similarly visualized by immunohistology using an antiserum specific for the microtubule-associated proteins. Surprisingly, the morphology of the Purkinje cell dendritic arborization also appeared unaltered in the hypothyroid mice. The results suggest that the morphological development of the mouse cerebellum is relatively unaffected by hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Paramagnetic macrocyclic chelates show promise as magnetic resonance (MR) imaging contrast agents due to stability and relaxivity comparable to those of DTPA-type chelates. For the three copper and manganese macrocyclic complexes studied in aqueous solution, T1 and T2 relaxivities ranged from 0.14 to 5.88 mM-1sec-1 at 6.25 MHz. In rats, the intravenous administration of 16 mumol/kg of Mn(cyclam) caused the liver T1 relaxation rate to double at 15 minutes after injection. T1 measurements by pulsed MR imaging and manganese analyses on excised tissue showed that both relaxation rate (1/T1) and manganese content of liver and kidney increase linearly with the dosage of Mn(cyclam). The linear relationship between 1/T1 and manganese content can be considered an "in tissue" relaxivity plot for the agent. The resulting relaxivity is 54 mM-1sec-1 in liver, compared with 3.1 mM-1sec-1 in aqueous solution. Although this work is preliminary, the implication for medical MR imaging applications is that macrocyclic contrast agents can be effective at approximately one-tenth the current typical dose used for gadolinium DTPA. 相似文献
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Semi-empirical (CNDO) molecular orbital calculations, based on a previously reported ammonia-amine model system, were performed on an extended series of methyl-, ethyl-, and propylamines as models for the analgesic receptor. Methyl-, dimethyl-, and trimethylamines were chosen to represent the opiate molecules. Interatomic distances were varied within normally expected biological values. The results for the larger systems are similar to more elaborate calculations previously reported using smaller molecules. At internuclear distances of greater than 0.275 nm, the potential energy curves had two minima. At 0.2731 nm, the optimized N-N distance, the "depth" of the minima in the potential energy curve were not as great. Energy differences as well as population differences suggest deviation from the currently stated clastic binding theories mechanism for the analgesic response of the tertiary amines. The dimethylamine energy profile and population data indicate that the hypothesis of N-demethylated opiate as the active molecule needs further consideration and investigation. Investigation of larger systems is also indicated to develop increasingly realistic models for the analgesic response. 相似文献