Neurochemical Research, Vol. 16, No. 8, 1991, pp. 843-847 Brief Fasting Decreases Protein Synthesis in the Brain of Adult Rats Y. ChereP, D. Attaix 2, D. Rosolowska-Huszcz 2, M. Arnal 2, and Y. Le Maho I (Accepted February 26, 1991) The influence of starvation on protein synthesis in the adult rat brain was studied in vivo by an intravenous injection of a flooding dose of unlabeled valine including a tracer dose of L-[3,4(n)- 3H]valine. Brief starvation (24 hours) induced a 20% decline in fractional and absolute rates of brain protein synthesis. This decline resulted from a 20% decrease in the efficiency of protein synthesis (Ixg protein synthesized per day per Izg RNA) whereas the capacity for protein synthesis (~g RNA per mg protein) was maintained. Prolonged starvation (5 days) was marked by no further significant changes in the fractional rate, absolute rate and efficiency of protein synthesis, whereas the capacity for protein synthesis decreased slightly. The relative contribution of brain to whole- body protein synthesis increased during fasting, and neither the protein nor the RNA brain content did change during the experiment. These results clearly indicate that brain proteins are spared in response to brief and prolonged food deprivation, and that brain protein synthesis is very sensitive to short-term fasting. KEY WORDS: Starvation~ protein turnover; large dose method; valine; RNA. INTRODUCTION The effects of undernutrition on protein metabolism in the brain of the developing rat have been investigated in some details (1). Brain from malnourished rats has lower weight, and lower protein and nucleic acid con- tents (2-4). This lower protein mass relative to control results from a decrease in the rate of protein synthesis exceeding that of protein degradation (5). On the other hand, adult rat brain is fairly resistant to the effects of nutritional deficiencies, its protein content remaining un- changed even after prolonged starvation (6-9). It may accordingly be expected that protein turnover in adult rat brain is weakly affected by fasting. Two groups stud- Laboratoire d'Etude des REgulations Physiologiques, associ6 ~ I'U- niversit6 Pasteur, Centre National de la Recherche Seientifique, 23 rue Becquerel, 67087 Strasbourg, France. 2 Laboratoire d'Etude du M6tabolisme Azot6, lnstitut National de la Recherche Agronomique, Theix, 63122 Ceyrat, France. 843 ied the effect of food deprivation on protein synthesis in the brain from mature rats. Garlick et al. (10) initially reported that the rate of protein synthesis decreases by 16% of the initial value after 2 days of starvation. In contrast, Preedy et al., in one report (11), found no change in protein synthesis of brains from overnight- fasted rats; in a second paper (12), however, they showed a 12% decline in brain protein synthesis after 24 hours of starvation but no change after 2 days. In view of these apparently discrepant reports, it was therefore necessary to reinvestigate the effect of starvation on protein synthesis in the adult rat brain and its possible changes during the course of a prolonged fast. In the present study, protein synthesis was mea- sured by the most reliable technique available in vivo, the flooding dose procedure, in which a large amount of unlabeled amino acid is co-injected with the tracer to rise tissue free amino acid concentrations and to equili- brate specific radioactivities in extra and intracellular amino acid pools (13). This technique has been previ- 0364-3190/91/0800-0843506.50/0 1991Plenum Publishing Corporation