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Abstract
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.