Garris D R
Cleveland Research Laboratory, Kansas City, MO 64131.
Brain Res. 1989 Oct 30;501(1):162-70. doi: 10.1016/0006-8993(89)91037-8.
The influence of the obese (ob/ob) and diabetes (db/db) genetic mutations on hypothalamic structure was investigated in C57BL/KsJ and C57BL/6J mice strains by morphometric analysis of medial basal nuclei which are recognized to possess glucoregulatory neurons. Brains were collected and prepared for histomorphometric analysis at selected times following the development of expressed obesity and diabetes (Type II, non-insulin dependent) syndromes in order to compare both the strain and genomic influences on neuronal viability in the hypothalamic ventromedial (VMH) and arcuate (ARC) nuclei of mutant and age-matched control mice. The severity of each syndrome was determined by monitoring the concomitant changes in body weight and blood glucose levels in all groups. Both (db/db) and (ob/ob) mutant C57BL/KsJ mice exhibited an increase in the number and distribution of degenerated neurons in the VMH and ARC nuclei relative to corresponding controls. The mutation-associated exacerbation of the normal age-related neuronal loss, as observed in control MBH nuclei, was temporally associated with the overt expression of the hyperglycemic component of the obese and diabetes syndromes in aging C57BL/KsJ mice. No temporal or causal relationships were noted between the enhanced rate of premature neuronal degeneration, and either body weight or blood glucose levels, in either (db/db) or (ob/ob) C57BL/6J mice relative to controls. These data suggest that the hyperglycemic condition which characterizes the (ob/ob) and (db/db) mutant C57BL/KsJ mice is causally associated with the pronounced, premature MBH neuronal degeneration in these mouse strains. Neuronal changes were not pronounced when the genetic mutations were expressed in C57BL/6J mice. The accompanying alterations in brain glucose metabolism, hormone sensitivity, bioamine content and function which are recognized to occur in these mutant C57BL/KsJ mice may be causally associated consequences of the observed changes in MBH structural integrity and neuronal competence, with the severity of the mutation-associated changes being related to genetic background of the murine strain.
通过对内侧基底部核进行形态测量分析，研究了肥胖（ob/ob）和糖尿病（db/db）基因突变对C57BL/KsJ和C57BL/6J小鼠品系下丘脑结构的影响，内侧基底部核被认为含有葡萄糖调节神经元。在显性肥胖和糖尿病（II型，非胰岛素依赖型）综合征出现后的选定时间收集大脑并进行组织形态测量分析，以比较品系和基因组对突变小鼠和年龄匹配对照小鼠下丘脑腹内侧（VMH）核和弓状（ARC）核中神经元活力的影响。通过监测所有组体重和血糖水平的伴随变化来确定每种综合征的严重程度。相对于相应对照，（db/db）和（ob/ob）突变型C57BL/KsJ小鼠在VMH和ARC核中退化神经元的数量和分布均增加。在对照的内侧基底部核中观察到的与突变相关的正常年龄相关神经元丢失的加剧，在时间上与衰老的C57BL/KsJ小鼠中肥胖和糖尿病综合征高血糖成分的明显表达相关。相对于对照，在（db/db）或（ob/ob）C57BL/6J小鼠中，未观察到过早神经元退化率增加与体重或血糖水平之间存在时间或因果关系。这些数据表明，以（ob/ob）和（db/db）突变型C57BL/KsJ小鼠为特征的高血糖状况与这些小鼠品系中明显的、过早的内侧基底部核神经元退化存在因果关系。当在C57BL/6J小鼠中表达基因突变时，神经元变化并不明显。在这些突变型C57BL/KsJ小鼠中公认发生的伴随脑葡萄糖代谢、激素敏感性、生物胺含量和功能的改变，可能是观察到的内侧基底部核结构完整性和神经元能力变化的因果相关后果，与突变相关变化的严重程度与小鼠品系的遗传背景有关。
