Hippocampal mTOR Dysregulation and Morphological Changes in Male Rats after Fetal Growth Restriction
Autor: | Charlotte Schömig, Laura Oberholz, Gregor Fink, Jenny Voggel, Maria Wohlfarth, Jörg Dötsch, Kai-Dietrich Nüsken, Eva Nüsken |
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Rok vydání: | 2022 |
Předmět: |
Male
Fetal Growth Retardation Nutrition and Dietetics Nutrition. Foods and food supply Placenta TOR Serine-Threonine Kinases low-protein diet FGR Placental Insufficiency Hippocampus Rats intrauterine stress IUGR Pregnancy mTOR signaling Animals TX341-641 Female placental insufficiency neurocognitive development perinatal programming Food Science |
Zdroj: | Nutrients; Volume 14; Issue 3; Pages: 451 Nutrients, Vol 14, Iss 451, p 451 (2022) |
ISSN: | 2072-6643 |
Popis: | 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. |
Databáze: | OpenAIRE |
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