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1 Institute of Health Biosciences, The University of Tokushima Graduate School
* To whom correspondence should be addressed. E-mail: rokutan16{at}basic.med.tokushima-u.ac.jp.
Caloric restriction (CR) is an effective method for prevention of age-associated diseases as well as overweight and obesity; however, there is controversy regarding the effects of dieting regimens on behavior. In this study, we investigated two different dieting regimens: repeated fasting and refeeding (RFR) and daily feeding of half the amount of food consumed by RFR mice (CR). CR and RFR mice had an approximate 20% reduction in food intake compared with control mice. Open field, light-dark transition, elevated plus maze, and forced swimming tests indicated that CR, but not RFR, reduced anxiety- and depressive-like behaviors, with a reduction peak on day 8. Using a mouse whole genome microarray, we analyzed gene expression in the prefrontal cortex, amygdala, and hypothalamus. In addition to the caloric restriction-responsive genes commonly modified by RFR and CR, each regimen differentially changed the expression of distinct genes in each region. The most profound change was observed in the amygdala of CR mice: 884 genes were specifically up-regulated. Ingenuity pathway analysis showed that these 884 genes significantly modified 9 canonical pathways in the amygdala.
-adrenergic and dopamine receptor signalings were the two top-scoring pathways. Quantitative RT-PCR confirmed the up-regulation of 6 genes in these pathways. Western blotting confirmed that CR specifically increased dopamine-and cAMP-regulated phosphoprotein (Darpp-32), a key regulation of dopamine receptor signaling, in the amygdala. Our results suggest that CR may change behavioral consequence through altered gene expression.
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