TY - JOUR
T1 - The frontal cortex IGF system is down regulated in the term, intrauterine growth restricted fetal baboon
AU - Xie, L.
AU - Antonow-Schlorke, I.
AU - Schwab, M.
AU - McDonald, T. J.
AU - Nathanielsz, P. W.
AU - Li, C.
N1 - Funding Information:
This work was supported by NICHD HD 21350-20 . We are grateful for technical assistance from Greg Langone and Sue Jenkins with this difficult model and to Karen Moore for her help with the manuscript.
PY - 2013/10
Y1 - 2013/10
N2 - Objective: The IGF system exerts systemic and local actions during development. We previously demonstrated that fetal cerebral cortical IGF1 is reduced at 0.5 gestation in our IUGR baboon nonhuman primate model. We hypothesized that by term protein expression of several key IGF system stimulatory peptide pathway components and downstream nutrient signaling effectors of IGF, mammalian target of rapamycin (mTOR) and S6, would decrease, indicating reduced cellular nutrient uptake and protein synthesis. Design: We fed 7 control baboons ad libitum while 6 baboons ate a globally reduced diet (70% of feed eaten by controls) from 0.16 gestation through pregnancy that produces IUGR. Fetuses were removed at Cesarean section at 0.9 gestation. Frontal cortex sections were stained for IGFI, IGFII, IGFRI, IGFR2, IGFBP2, 3, 5 and 6, and mTOR and ribosomal protein S6 and double stained with NeuN a neuron-specific nuclear antigen. Results: All proteins stained neuronal cytoplasm except IGFRI which showed only glial cell cytoplasmic and blood vessel staining. IUGR fetuses showed decreased frontal cortical immunoreactive IGFI, IGFII, IGFRI, IGFBP2, 5 and 6, and mTOR and S6 (p<0.05). IGFBP3 increased (p<0.05) and IGFR2 was unchanged (p>0.05). There were no differences between male and female fetal brains. Conclusions: When fetal nutrient availability is decreased, IUGR down regulates the IGF system and its mTOR signaling pathway in the fetal frontal cortex coincident with slowed growth. These findings emphasize the importance of the local tissue IGF system in fetal primate brain development.
AB - Objective: The IGF system exerts systemic and local actions during development. We previously demonstrated that fetal cerebral cortical IGF1 is reduced at 0.5 gestation in our IUGR baboon nonhuman primate model. We hypothesized that by term protein expression of several key IGF system stimulatory peptide pathway components and downstream nutrient signaling effectors of IGF, mammalian target of rapamycin (mTOR) and S6, would decrease, indicating reduced cellular nutrient uptake and protein synthesis. Design: We fed 7 control baboons ad libitum while 6 baboons ate a globally reduced diet (70% of feed eaten by controls) from 0.16 gestation through pregnancy that produces IUGR. Fetuses were removed at Cesarean section at 0.9 gestation. Frontal cortex sections were stained for IGFI, IGFII, IGFRI, IGFR2, IGFBP2, 3, 5 and 6, and mTOR and ribosomal protein S6 and double stained with NeuN a neuron-specific nuclear antigen. Results: All proteins stained neuronal cytoplasm except IGFRI which showed only glial cell cytoplasmic and blood vessel staining. IUGR fetuses showed decreased frontal cortical immunoreactive IGFI, IGFII, IGFRI, IGFBP2, 5 and 6, and mTOR and S6 (p<0.05). IGFBP3 increased (p<0.05) and IGFR2 was unchanged (p>0.05). There were no differences between male and female fetal brains. Conclusions: When fetal nutrient availability is decreased, IUGR down regulates the IGF system and its mTOR signaling pathway in the fetal frontal cortex coincident with slowed growth. These findings emphasize the importance of the local tissue IGF system in fetal primate brain development.
KW - Baboon fetus
KW - Binding proteins
KW - Brain
KW - IGF
KW - IGF receptors
KW - IGFI
KW - IUGR
KW - MTOR
KW - S6
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U2 - 10.1016/j.ghir.2013.07.003
DO - 10.1016/j.ghir.2013.07.003
M3 - Article
C2 - 23911858
AN - SCOPUS:84882878544
VL - 23
SP - 187
EP - 192
JO - Growth Hormone and IGF Research
JF - Growth Hormone and IGF Research
SN - 1096-6374
IS - 5
ER -