title: Expression of apoptosis-regulatory genes in the hippocampus of rat neonates born to mothers with diabetes.
abstract: Diabetes during pregnancy impairs the development of the central nervous system (CNS) and causes cognitive and behavioral abnormalities in offspring. However, the exact mechanism by which the maternal diabetes affects the development of the brain remains to be elucidated. The aim of the present study was to investigate the effects of maternal diabetes in pregnancy on the expression of Bcl-2 and Bax genes and the numerical density of degenerating dark neurons (DNs) in the hippocampus of offspring at the first postnatal two weeks. Wistar female rats were maintained diabetic from a week before pregnancy through parturition and male offspring was sacrificed at P0, P7, and P14. Our findings demonstrated a significant down-regulation in the hippocampal expression of Bcl-2 in the diabetic group newborns (P < 0.05). In contrast, the mRNA expression of Bax was markedly up-regulated in the offspring born to diabetic dams at all of studied time-points (P < 0.05). Moreover, we found a striking increase in the numerical density of DNs in the various subfields of hippocampus of diabetic group pups (P < 0.05). The results of the present study revealed that maternal hyperglycemia during gestational period may result in disturbances in the expression of Bcl-2 and Bax genes as two important genes in neuronal apoptosis regulation and induces the production of DNs in the developing hippocampus of neonatal rats. These disturbances may be a reason for the cognitive, structural, and behavioral anomalies observed in offspring born to diabetic mothers. Furthermore, the control of maternal glycaemia by insulin administration in most cases normalized these negative impacts.
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.|Medical Genetic Research Center (MGRC), School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Haghir
authors.affiliation: Department of Anatomical Sciences, School of Medicine, Birjand University of Medical Sciences, Ghaffari St., Birjand, Iran. javadhami@gmail.com.|Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran. javadhami@gmail.com.
authors.forename: Javad
authors.initials: J
authors.lastname: Hami
authors.affiliation: Department of Anatomical Sciences, School of Medicine, Birjand University of Medical Sciences, Ghaffari St., Birjand, Iran.
authors.forename: Nassim
authors.initials: N
authors.lastname: Lotfi
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Peyvandi
authors.affiliation: Microanatomy Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Simagol
authors.initials: S
authors.lastname: Ghasemi
authors.affiliation: Department of Public Health, Deputy of Research and Technology, Research Centre of Experimental Medicine, Birjand University of Medical Sciences, Birjand, Iran.
authors.forename: Mehran
authors.initials: M
authors.lastname: Hosseini
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000473:pathology*; D016640:Diabetes, Gestational / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D019254:Genes, bcl-2; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D001786:Blood Glucose; D051028:bcl-2-Associated X Protein
keywords: Apoptosis regulatory genes; Dark neuron; Hippocampus; Maternal diabetes; Rat neonate