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Published on: November 20, 2015
Hippocampal mTOR Dysregulation and Morphological Changes in Male Rats after Fetal Growth Restriction
Charlotte Schömig1, Laura Oberholz1, Gregor Fink1
1Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany.
Insights
Fetal growth restriction (FGR) impacts male rat brain development, altering hippocampal cell density and mTOR signaling differently based on the cause. Long-term effects on mTOR signaling and Tau phosphorylation were not observed.
Area of Science:
- Neuroscience
- Developmental Biology
- Reproductive Medicine
Background:
- Fetal growth restriction (FGR) is associated with long-term neurocognitive deficits, particularly in males.
- Understanding the mechanisms behind FGR-induced brain alterations is crucial for potential interventions.
Purpose of the Study:
- To investigate the effects of different FGR models on hippocampal cellular composition and mTOR signaling in male rat offspring.
- To determine if prenatal insults lead to lasting changes in mTOR signaling and Tau phosphorylation.
Main Methods:
- FGR was induced in rats via low-protein diet, placental insufficiency, or intrauterine surgical stress.
- Hippocampal cellular density, mTOR signaling, and Tau phosphorylation were assessed at specific postnatal days (PND 1, 12, and 180).
Main Results:
- Low-protein diet reduced dentate gyrus cell density; surgical stress increased CA2 subregion cell density.
- Placental insufficiency and surgical stress increased mTOR activation during early development (PND 1 and 12).
- No significant long-term changes in mTOR signaling or Tau phosphorylation were observed by PND 180.
Conclusions:
- The cause of FGR influences hippocampal cellular proliferation and mTOR signaling pathways differently.
- Prenatal insults can lead to distinct early-life hippocampal alterations, but long-term molecular changes were not evident in this study.
Abstract:
Fetal growth restriction (FGR) has been linked to long-term neurocognitive impairment, especially in males. To determine possible underlying mechanisms, we examined hippocampal cellular composition and mTOR signaling of male rat FGR offspring during main brain growth and development (postnatal days (PND) 1 and 12). FGR was either induced by a low-protein diet throughout pregnancy, experimental placental insufficiency by bilateral uterine vessel ligation or intrauterine stress by "sham" operation. Offspring after unimpaired gestation served as common controls. Low-protein diet led to a reduced cell density in the molecular dentate gyrus subregion, while intrauterine surgical stress was associated with increased cell density in the cellular CA2 subregion. Experimental placental insufficiency caused increased mTOR activation on PND 1, whereas intrauterine stress led to mTOR activation on PND 1 and 12. To determine long-term effects, we additionally examined mTOR signaling and Tau phosphorylation, which is altered in neurodegenerative diseases, on PND 180, but did not find any changes among the experimental groups. Our findings suggest that hippocampal cellular proliferation and mTOR signaling are dysregulated in different ways depending on the cause of FGR. While a low-protein diet induced a decreased cell density, prenatal surgical stress caused hyperproliferation, possibly via increased mTOR signaling.
