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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Postnatal high-protein diet improves learning and memory in premature rats via activation of mTOR signaling
Zhi-Wen Su1, Jia-Yi Liao2, Hui Zhang1
1Department of Pediatrics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhong, China.
Insights
A high-protein diet improved spatial learning and memory in premature rats by upregulating mammalian target of rapamycin (mTOR) signaling, specifically the mTOR/p70S6K pathway, restoring cognitive function.
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Premature birth can lead to cognitive deficits, including impaired spatial learning and memory.
- Mammalian target of rapamycin (mTOR) signaling plays a crucial role in neuronal development and synaptic plasticity.
- Dietary interventions are being explored to mitigate developmental impairments.
Purpose of the Study:
- To investigate the effect of a high-protein diet (HPD) on spatial learning and memory in premature rats.
- To determine if HPD modulates the mammalian target of rapamycin (mTOR) signaling pathway in the hippocampus.
- To assess the potential of HPD to restore cognitive deficits associated with prematurity.
Main Methods:
- Premature and full-term Sprague-Dawley rat pups were fed either a normal (18% protein) or HPD (30% protein) for 6 or 8 weeks post-weaning.
- Spatial learning and memory were evaluated using the Morris water maze test.
- Hippocampal mTOR signaling pathway components (p70S6K and 4EBP1 phosphorylation) were analyzed via western blotting.
Main Results:
- Premature rats exhibited lower spatial memory than full-term rats at 6 weeks, correlating with reduced hippocampal p70S6K and 4EBP1 phosphorylation.
- Spatial memory significantly improved in premature rats fed an HPD for 8 weeks compared to those on a normal diet.
- HPD consumption normalized hippocampal p70S6K and 4EBP1 phosphorylation levels in premature rats to levels seen in full-term rats on an HPD.
Conclusions:
- Long-term HPD consumption can ameliorate spatial learning and memory impairments in pre-term rats.
- The restorative effects are mediated through the upregulation of the mTOR/p70S6K signaling pathway in the hippocampus.
- Dietary protein intake is a potential therapeutic strategy for cognitive deficits in premature offspring.
Purpose:
The 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.
Methods:
Pre- 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.
Results:
Spatial 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.
Conclusion:
Long-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.
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