BACKGROUND: Recent data suggest that insulin-like growth factor (IGF)-1 
resistance in neurons prolongs longevity. In C. elegans this effect is mediated 
via DAF-16 the ortholog of the mammalian FoxO transcription factors. 3 different 
FoxO transcription factors (FoxOs) are expressed in rodent CNS: FoxO1, FoxO3a 
and FoxO6.
METHODS: To define whether the different FoxOs are region-, sex- and 
age-specifically expressed, we analyzed FoxO mRNA levels in different brain 
regions from 6, 16, 60 and 100 weeks old mice using realtime-PCR. In addition, 
we fed mice a high fat diet (HFD) to experimentally induce obesity and diabetes 
and analyzed FoxO mRNA in the different brain regions.
RESULTS: Interestingly, FoxO1 was predominantly expressed in the hippocampus 
whereas FoxO3a was quantitatively the most abundant FoxO in the neocortex. 
During aging, FoxO1 expression peaked in all brain regions at 16 weeks and FoxO6 
showed its highest expression at 60 weeks in the parietal and occipital cortex. 
In 6 weeks old mice FoxO6 expression was higher in male compared to female mice 
in the hippocampus and all cortical regions. Surprisingly, in HFD animals FoxO3a 
was significantly less expressed in the cerebellum and all cortical regions 
compared to control animals. Even more dramatic, FoxO6 expression dropped about 
80% in all brain regions in response to HFD.
CONCLUSION: Thus, FoxOs in the CNS showed a highly distinct expression, which in 
addition was age- and sex-dependent. In contrast to FoxO1, FoxO3a and FoxO6 were 
specifically diminished in the CNS of HFD animals possibly contributing to the 
reduced lifespan observed in these animals.