Morphometric analysis of obesity (ob/ob)- and diabetes (db/db)-associated hypothalamic neuronal degeneration in C57BL/KsJ mice.
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.
Garris
D R
DR
Cleveland Research Laboratory, Kansas City, MO 64131.
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000473:pathology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002452:Cell Count; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration; D009765:Obesity / Q000473:pathology*; D014697:Ventromedial Hypothalamic Nucleus / Q000473:pathology*
D001786:Blood Glucose