Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; Cellular and Molecular Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran; Institute for Anatomy and Cell Biology, University Medicine Greifswald, Greifswald, Germany.
J Chem Neuroanat. 2021 Jul;114:101946. doi: 10.1016/j.jchemneu.2021.101946. Epub 2021 Mar 18.
Maternal diabetes during pregnancy affects the development of hippocampus in the offspring. Brain-derived neurotrophic factor (BDNF) has received increasing attention for its role in regulating the survival and differentiation of neuronal cells in developing and adult brain. In the current study, we evaluated the effects of maternal diabetes and insulin treatment on expression and distribution pattern of BDNF in the hippocampus of neonatal rats at the first two postnatal weeks. We found no differences in hippocampal expression of BDNF between diabetics with normal control or insulin treated neonatal rats at postnatal day (P0) (P > 0.05 each). Nevertheless, there was a marked BDNF downregulation in both sides' hippocampi of male/female diabetic group in two-week-old offspring (P ≤ 0.05 each). Furthermore, the numerical density of BDNF cells was significantly reduced in the right/left dentate gyrus (DG) of male and female newborns born to diabetic animals at all studied postnatal days (P ≤ 0.05 each). In addition, a lower number of reactive cells have shown in the all hippocampal subareas in the diabetic pups at P14 (P ≤ 0.05 each). Our results have demonstrated that the insulin-treatment improves some of the negative impacts of diabetes on the expression of hippocampal BDNF in the newborns. We conclude that diabetes in pregnancy bilaterally disrupts the expression of BDNF in the hippocampus of the both male and female newborns at early postnatal days. In addition, good glycemic control by insulin in the most cases is sufficient to prevent the alterations in expression of BDNF protein in developing hippocampus.
孕期母体糖尿病会影响后代海马体的发育。脑源性神经营养因子(BDNF)因其在调节发育中和成年大脑中神经元细胞的存活和分化方面的作用而受到越来越多的关注。在本研究中,我们评估了母体糖尿病及其胰岛素治疗对新生大鼠前两周海马体中 BDNF 表达和分布模式的影响。我们发现,糖尿病大鼠的海马体 BDNF 表达与正常对照组或胰岛素治疗组的新生大鼠在出生后第 0 天(P0)没有差异(每个组的 P 值均>0.05)。然而,在两周龄的雄性和雌性新生鼠中,糖尿病组双侧海马体的 BDNF 表达均明显下调(每个组的 P 值均≤0.05)。此外,在糖尿病动物所生雄性和雌性新生儿的双侧齿状回(DG)中,BDNF 细胞的数量密度在所有研究的出生后天数均显著降低(每个组的 P 值均≤0.05)。此外,在 P14 时,糖尿病幼鼠的所有海马区的反应性细胞数量均减少(每个组的 P 值均≤0.05)。我们的结果表明,胰岛素治疗改善了糖尿病对新生鼠海马体 BDNF 表达的一些负面影响。我们得出结论,孕期糖尿病双侧破坏了雄性和雌性新生鼠早期海马体中 BDNF 的表达。此外,在大多数情况下,通过胰岛素实现良好的血糖控制足以防止发育中的海马体中 BDNF 蛋白表达的改变。