To explore mechanisms underlying central nervous system
(CNS) complications in diabetes, we examined hippocampal neuronal
apoptosis and loss, and the effect of C-peptide replacement
in type 1 diabetic BB/W rats. Apoptosis was demonstrated after
8 months of diabetes, by DNA fragmentation, increased number of
apoptotic cells, and an elevated ratio of Bax/Bcl-xL, accompanied
by reduced neuronal density in the hippocampus. No apoptotic activity
was detected and neuronal density was unchanged in 2-month
diabetic hippocampus, whereas insulin-like growth factor (IGF) activities
were impaired. In type 1 diabetic BB/W rats replaced with
C-peptide, no TdT-mediated dUTP nick-end labeling (TUNEL)-
positive cells were shown and DNA laddering was not evident in
hippocampus at either 2 or 8 months. C-peptide administration prevented
the preceding perturbation of IGF expression and reduced
the elevated ratio of Bax/Bcl-xL. Our data suggest that type 1 diabetes
causes a duration-dependent programmed cell death of the
hippocampus, which is partially prevented by C-peptide.
