Research ReportPostnatal high-protein diet improves learning and memory in premature rats via activation of mTOR signaling

•First demonstration of a link between preterm and mTOR signaling pathway.•Premature delivery might inhibit the activity of mTOR signaling pathway.•High-protein diet had no impact on the learning memory of premature rats during the early development.•Long-term high-protein diet might increase the activity of mTOR signaling pathway in premature rats.

PurposeThe present study investigated whether a high-protein diet affects spatial learning and memory in premature rats via modulation of mammalian target of rapamycin (mTOR) signaling.MethodsPre- and full-term Sprague-Dawley pups were fed a normal (18% protein) or high-protein (30% protein) diet (HPD) for 6 or 8 weeks after weaning. Spatial learning and memory were tested in the Morris water maze at week 6 and 8. The activation of mTOR signaling pathway components was evaluated by western blotting.ResultsSpatial memory performance of premature rats consuming a normal and HPD was lower than that of full-term rats on the same diet at 6 weeks, and was associated with lower levels of ribosomal protein S6 kinase p70 subtype (p70S6K) and initiation factor 4E-binding protein 1 (4EBP1) phosphorylation in the hippocampus. Spatial memory was improved in 8-week-old premature rats on an HPD as compared to those on a normal diet. Premature rats on an HPD had p70S6K and 4EBP1 phosphorylation levels in the hippocampus that were comparable to those of full-term rats on an HPD.ConclusionLong-term consumption of a protein-rich diet can restore the impairment in learning and memory in pre-term rats via upregulation of mTOR/p70S6K signaling.