the survey of the effect of Insulin therapy on gene expression and distribution pattern of BDNF protein in the hippocampus of newborns born to diabetic rats

Background and Aim : Gestational diabetes is one of the most common disorders during pregnancy, disturbing fetus development which might ultimately lead to the perinatal or newborn mortality. Hippocampus is a part of the brain which has a major role in memory formation and one of the most vulnerable brain components sensitive to blood sugar fluctuations. Brain-derived nephrotic factor (BDNF) is a member of nephrotic factors which has a role to play in regulating the survival and differentiation of neuronal cells during development. Hippocampus is one of the major sites of BDNF function, and as growing evidence indicates, this factor is vital in learning and memory formation. This study aims to evaluate the effects of Streptozotocin-induced type 1 maternal diabetes on distribution pattern and also the expression of BDNF in different areas of the hippocampus in newborn rats.Methods : 18 pregnant Wistar rats were obtained and then randomly categorized into 3 groups: 1. The diabetic group (STZ-D): 60mg/kg of STZ was solubilized in normal saline and injected intraperitoneally to rats. 2. The diabetic group treated with insulin (STZ-INS): after the diabetic model confirmation, the rats were treated with 4-6 insulin units subcutaneously twice a day for two weeks. During this procedure, the blood sugar level was monitored. 3. The control group (CON): there was an equal number to that of the diabetic group which the treated intraperitoneally with normal saline. Their blood sugar level was also monitored using a glucometer. At the end of the pregnancy, the newborns were anesthetized and after the brain and hippocampus dissection the distribution pattern and also the expression of BDNF in different areas of the hippocampus in newborn rats was evaluated using immunohistochemistry and real-time PCR, respectively.Results : The results of this study demonstrated that there was no significant difference regarding the expression of BDNF mRNA in the newborns of diabetic mothers after 1, 7 and 14 days of their birth compared to their control group counterparts (P> 0.05). Furthermore, the BDNF protein expression was significantly declined across the hippocampus in the newborns of diabetic mothers at days 1, 7 and 14 after birth (P<0.05). Additionally, it was found that using insulin possibly increase the protein expression of BDNF and also reduces its negative impact on the newborns.Conclusion : The results of this study for the first time showed that gestational diabetes reduces the expression levels of BDNF protein across the hippocampus of the newborns. On the other hand, controlling the levels of blood sugar in diabetic mothers using insulin can reduce these complications.

Keywords:

Gestational diabetes , Hippocampus , BDNF , Newborn rats