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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Apr 15, 2015; 6(3): 412-422
Published online Apr 15, 2015. doi: 10.4239/wjd.v6.i3.412
Some of the experimental and clinical aspects of the effects of the maternal diabetes on developing hippocampus
Javad Hami, Fatemeh Shojae, Saeed Vafaee-Nezhad, Nasim Lotfi, Hamed Kheradmand, Hossein Haghir
Javad Hami, Fatemeh Shojae, Saeed Vafaee-Nezhad, Nasim Lotfi, Department of Anatomy, School of Medicine, Birjand University of Medical Sciences, Birjand 97178, Iran
Nasim Lotfi, Hossein Haghir, Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad 91857, Iran
Hamed Kheradmand, Hazrat Rasoul Hospital, Tehran University of Medical Sciences, Tehran 19168, Iran
Hossein Haghir, Medical Genetic Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad 91857, Iran
Author contributions: All authors contributed to this manuscript.
Conflict-of-interest: All authors claim no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hossein Haghir, MD, PhD, Department of Anatomy and Cell Biology, School of Medicine, Mashdad University of Medical Sciences, Azadi Square, Mashhad 91857, Iran. haghirh@mums.ac.ir
Telephone: +98-513-8002486 Fax: +98-513-8002486
Received: August 27, 2014
Peer-review started: August 31, 2014
First decision: October 14, 2014
Revised: December 22, 2014
Accepted: January 9, 2015
Article in press: January 12, 2015
Published online: April 15, 2015
Abstract

Diabetes mellitus during pregnancy is associated with an increased risk of multiple congenital anomalies in progeny. There are sufficient evidence suggesting that the children of diabetic women exhibit intellectual and behavioral abnormalities accompanied by modification of hippocampus structure and function. Although, the exact mechanism by which maternal diabetes affects the developing hippocampus remains to be defined. Multiple biological alterations, including hyperglycemia, hyperinsulinemia, oxidative stress, hypoxia, and iron deficiency occur in pregnancies with diabetes and affect the development of central nervous system (CNS) of the fetus. The conclusion from several studies is that disturbance in glucose and insulin homeostasis in mothers and infants are major teratogenic factor in the development of CNS. Insulin and Insulin-like growth factor-1 (IGF-1) are two key regulators of CNS function and development. Insulin and IGF-1 receptors (IR and IGF1R, respectively) are distributed in a highly specific pattern with the high density in some brain regions such as hippocampus. Recent researches have clearly established that maternal diabetes disrupts the regulation of both IR and IGF1R in the hippocampus of rat newborn. Dissecting out the mechanisms responsible for maternal diabetes-related changes in the development of hippocampus is helping to prevent from impaired cognitive and memory functions in offspring.

Keywords: Maternal diabetes, Cognition complications, Teratogenic factor, Hippocampus

Core tip: Diabetes mellitus is the most seriously metabolic condition in pregnancy that affects the hippocampal development and function of the offspring. Multiple biological alterations, including hyperglycemia and hyperinsulinemia are occurring in maternal diabetes and impair the neurodevelopment of the fetus. Insulin-like growth factor-1 (IGF-1) and insulin are important regulators of development of central nervous system. It has clearly showed that maternal diabetes disturb the regulation of both insulin receptors and IGF-1 receptors in the hippocampus of rat newborn. This article is a brief review of the literatures that suggests a probable mechanism of how diabetes during pregnancy affects the hippocampus development in the offspring.