Garris D R
Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City 64108, USA.
Brain Res Dev Brain Res. 1995 Nov 21;89(2):314-9. doi: 10.1016/0165-3806(95)00121-s.
Developmental and diabetes-associated changes in regional brain norepinephrine (NE) concentrations, and the influence of estradiol (E) and progesterone (P) on NE levels, were correlated with changes in blood glucose levels and body weight (obesity) in developing 4-16-week-old C57BL/KsJ (db/db) mice relative to corresponding age-matched control (+/?) parameters. Regional brain (i.e. amygdala, hypothalamus and medulla) NE levels were determined by high performance liquid chromatography. The (db/db) mice exhibited overt hyperglycemia and obesity relative to controls between 4 and 16 weeks of age. Hypothalamic NE levels in diabetics were chronically elevated as compared to those of age-matched controls by 8 weeks of age, and remained elevated through 16 weeks of age. Regional amygdaloid and medullary NE concentrations were comparable in (+/?) and (db/db) groups by 16 weeks. E-treatments normalized (db/db) hypothalamic NE concentrations to control levels between 8 and 16 weeks of age, but had no effect on amygdaloid or medullary values. In contrast, in 16 week old (db/db) mice, P-treatments elevated hypothalamic and medullary NE levels compared to controls and expected diabetic levels. These data demonstrate that a marked modification in regional brain NE concentrations occurs in association with the overt expression of the diabetes mutation during development in this species. Observed changes in adrenergic influences in specific CNS loci may be therapeutically modulated by ovarian steroid hormones, especially in the hypothalamic locus which is recognized to possess steroid-concentrating neurons. The observed normalization of regional brain NE concentrations by E-therapy may be causally related to the ovarian steroid-modulation of overt hyperglycemia and diabetes-associated neuronal degeneration in (db/db) mice.
在4至16周龄的C57BL/KsJ（db/db）发育小鼠中，将区域脑去甲肾上腺素（NE）浓度的发育性和糖尿病相关变化，以及雌二醇（E）和孕酮（P）对NE水平的影响，与血糖水平和体重（肥胖）变化相关联，并与相应年龄匹配的对照（+/？）参数进行比较。通过高效液相色谱法测定区域脑（即杏仁核、下丘脑和延髓）NE水平。在4至16周龄时，（db/db）小鼠相对于对照表现出明显的高血糖和肥胖。与年龄匹配的对照相比，糖尿病小鼠下丘脑NE水平在8周龄时长期升高，并在16周龄时一直保持升高。到16周时，（+/？）组和（db/db）组的区域杏仁核和延髓NE浓度相当。E治疗使（db/db）小鼠下丘脑NE浓度在8至16周龄时恢复到对照水平，但对杏仁核或延髓的值没有影响。相比之下，在16周龄的（db/db）小鼠中，P治疗使下丘脑和延髓NE水平相对于对照和预期的糖尿病水平升高。这些数据表明，在该物种发育过程中，随着糖尿病突变的明显表达，区域脑NE浓度发生了显著改变。在特定中枢神经系统位点观察到的肾上腺素能影响变化可能受到卵巢甾体激素的治疗性调节，特别是在下丘脑位点，该位点被认为拥有甾体浓缩神经元。通过E治疗观察到的区域脑NE浓度正常化可能与卵巢甾体对（db/db）小鼠明显高血糖和糖尿病相关神经元变性的调节有因果关系。
