| Abstrakt: |
Food restriction increases life-span in rodents. With regard to the central nervous system, underfeeding has been shown to have beneficial effects on synaptic transmission in old rats. However, the molecular events underlying functional changes in the brains of food-restricted rats are largely unknown. In the present study the levels of fibronectin mRNA containing the alternatively spliced segment V (FN-V+) as well as the levels of FN mRNA containing the alternatively spliced segment EIIIB (FN-EIIIB+), were examined by RNA gel blot hybridization in the brains of 3-day-old, 24-day-old, 10-month-old, 18-month-old, 30-month-old ad libitum (AL) fed, 30-month-old food-restricted (FR), and 35-37-month-old, FR rats. The hybridization signal for the FN-EIIIB+ mRNA was relatively abundant at early postnatal stages but very few transcripts were detected in the brains of adult, AL rats. The transcripts coding for FN-V+ mRNA were moderately expressed in the brains of 3-day-old, 24-day-old, 10-month-old, and 18-month-old rats. However, the FN-V+ mRNA signal was then prominently increased (approx. 3-fold) in the brains of the 30-month-old, AL rats vs. 10-month-old, AL rats, and further increased (approx. 2-fold) in the brains of 30-month-old, FR, as compared to 30-month-old, AL rats. However, the levels of FN-V+ mRNA were slightly decreased in the brains of very old (35-37-month) FR rats vs. 30-month-old FR rats. The distribution of fibronectin messenger RNA and protein was also investigated by non-radioactive in situ hybridization and immunohistochemistry, respectively. The most prominent expression of FN-V+ messenger RNA was seen in neurons of the hippocampus, including the granule cells of the dentate gyrus, and in layers III and V of the cortex of 30-month-old, FR rats. FN immunostaining closely paralleled the distribution of FN mRNA and was confined to the neuronal cell periphery. The upregulation of fibronectin gene expression upon exposure to glucocorticoids is well documented. Prolonged food restriction, acting as a stress factor, combined with decreased plasticity of glucocorticoid regulatory responses in the aged rats could cause an increase in the levels of FN mRNA and protein in the brains of old, FR rats. Since FN has been shown to provide an adhesive substrate for extending neurites, we conclude that food restriction may potentiate synaptic plasticity, via glucocorticoid receptor binding elements of the FN gene, in the brains of old rats. |
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