title: Effects of streptozotocin-induced type 1 maternal diabetes on PI3K/AKT signaling pathway in the hippocampus of rat neonates.
abstract: Diabetes in pregnancy impairs hippocampus development in offspring, leading to behavioral problems and learning deficits. Phosphatidylinositol 3-kinase/protein kinase B (PKB/Akt) signaling pathway plays a pivotal role in the regulation of neuronal proliferation, survival and death. The present study was designed to examine the effects of maternal diabetes on PKB/Akt expression and phosphorylation in the developing rat hippocampus. Wistar female rats were maintained diabetic from a week before pregnancy through parturition and male offspring was killed at first postnatal day (P1). The hippocampal expression and phosphorylation level of PKB/Akt, one of the key molecules in PI3K/AKT signaling pathway, was evaluated using real-time polymerase chain reaction (PCR) and western blot analysis. We found a significant bilateral downregulation of AKT1 gene expression in the hippocampus of pups born to diabetic mothers (p < 0.05). Interestingly, our results revealed a marked upregulation of Akt1 gene in insulin-treated group compared with other groups (p < 0.05). The western blot analysis also showed the reduction of phosphorylation level of all AKT isoforms in both diabetic and insulin-treated groups compared with control (p < 0.05). Moreover, the results showed a significant increase in phosphorylation level of AKT in insulin-treated group compared with the diabetic group. These results represent that diabetes during pregnancy strongly influences the regulation of PKB/AKT in the developing rat hippocampus. Furthermore, although the control of glycemia by insulin administration is not sufficient to prevent the alterations in PKB/Akt expression, it modulates the phosphorylation process, thus ultimately resulting in a situation comparable to that found in the normal condition.
authors.affiliation: a Department of Anatomical Sciences , Faculty of Medicine, Birjand University of Medical Sciences , Birjand , Iran .
authors.forename: Javad
authors.initials: J
authors.lastname: Hami
authors.affiliation: b Medical Genetics Research Center (MGRC), School of Medicine, Mashhad University of Medical Sciences (MUMS) , Mashhad , Iran .|c Department of Medical Genetics , Faculty of Medicine, Mashhad University of Medical Sciences (MUMS) , Mashhad , Iran .
authors.forename: Mohammad-Amin
authors.initials: MA
authors.lastname: Kerachian
authors.affiliation: b Medical Genetics Research Center (MGRC), School of Medicine, Mashhad University of Medical Sciences (MUMS) , Mashhad , Iran .|c Department of Medical Genetics , Faculty of Medicine, Mashhad University of Medical Sciences (MUMS) , Mashhad , Iran .
authors.forename: Razieh
authors.initials: R
authors.lastname: Karimi
authors.affiliation: b Medical Genetics Research Center (MGRC), School of Medicine, Mashhad University of Medical Sciences (MUMS) , Mashhad , Iran .|d Department of Anatomy and Cell Biology , School of Medicine, Mashhad University of Medical Sciences (MUMS) , Mashhad , Iran , and.
authors.forename: Hossein
authors.initials: H
authors.lastname: Haghir
authors.affiliation: b Medical Genetics Research Center (MGRC), School of Medicine, Mashhad University of Medical Sciences (MUMS) , Mashhad , Iran .|c Department of Medical Genetics , Faculty of Medicine, Mashhad University of Medical Sciences (MUMS) , Mashhad , Iran .|e Molecular Medicine Research Department, Iranian Academic Center for Education, Culture and Research (ACECR) , Khorasan Razavi Branch , Mashhad , Iran.
authors.forename: Ariane
authors.initials: A
authors.lastname: Sadr-Nabavi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin
chemical_list: D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D013311:Streptozocin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Maternal diabetes; PI3K/AKT signaling pathway; PKB/AKT; hippocampus