Intranasal insulin reverts central pathology and cognitive impairment in diabetic mother offspring.
Intranasal insulin reverts central pathology and cognitive impairment in diabetic mother offspring.
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DOI：
10.1186/s13024-017-0198-4
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发表时间：
2017-08-02
影响因子：
15.1
通讯作者：
Garcia-Alloza M
中科院分区：
文献类型：
--
作者：
Ramos-Rodriguez JJ;Sanchez-Sotano D;Doblas-Marquez A;Infante-Garcia C;Lubian-Lopez S;Garcia-Alloza M
糖尿病母亲后代（DMO）的不良反应是发病率增加的主要问题。其中，DMO的慢性中枢并发症仍然知之甚少，在极端情况下，糖尿病基本上可以作为妊娠期脑损伤。然而，DMO的治疗选择有限。因此，我们分析了中心的长期并发症的后代从CD 1糖尿病母亲治疗链脲佐菌素，以及可能逆转这些改变胰岛素给新生儿。在短期（P7）和成年早期（10周）评估了脑萎缩、神经元形态、tau蛋白磷酸化、增殖和神经发生，并在长期分析了认知功能。DMO的中枢并发症在成年期仍然可以检测到，包括由于突触丢失和神经元简化导致的皮质和海马变薄、tau蛋白过度磷酸化增加以及细胞增殖和神经发生减少。此外，母体糖尿病增加了后代对自发性中心出血、炎症和认知障碍的长期易感性。另一方面，脑室内胰岛素给药的新生儿显着减少观察到的变化。此外，非侵入性鼻内胰岛素逆转了中枢萎缩和tau蛋白过度磷酸化，挽救了中枢增殖和神经发生。血管损伤、炎症和认知改变也与非糖尿病小鼠的对应物相当，这支持了该途径进入中枢神经系统的实用性。我们的数据支持DMO中枢并发症的长期影响。此外，胰岛素治疗后观察到的改善为暴露于控制不良的妊娠期糖尿病的儿童打开了治疗替代品的大门，并且可能受益于更个性化的治疗。
Adverse effects in diabetic mothers offspring (DMO) are a major concern of increasing incidence. Among these, chronic central complications in DMO remain poorly understood, and in extreme cases, diabetes can essentially function as a gestational brain insult. Nevertheless, therapeutic alternatives for DMO are limited. Therefore, we have analyzed the central long-term complications in the offspring from CD1 diabetic mothers treated with streptozotozin, as well as the possible reversion of these alterations by insulin administration to neonates. Brain atrophy, neuronal morphology, tau phosphorylation, proliferation and neurogenesis were assessed in the short term (P7) and in the early adulthood (10 weeks) and cognitive function was also analyzed in the long-term. Central complications in DMO were still detected in the adulthood, including cortical and hippocampal thinning due to synaptic loss and neuronal simplification, increased tau hyperphosphorylation, and diminished cell proliferation and neurogenesis. Additionally, maternal diabetes increased the long-term susceptibility to spontaneous central bleeding, inflammation and cognition impairment in the offspring. On the other hand, intracerebroventricular insulin administration to neonates significantly reduced observed alterations. Moreover, non-invasive intranasal insulin reversed central atrophy and tau hyperphosphorylation, and rescued central proliferation and neurogenesis. Vascular damage, inflammation and cognitive alterations were also comparable to their counterparts born to nondiabetic mice, supporting the utility of this pathway to access the central nervous system. Our data underlie the long-term effects of central complications in DMO. Moreover, observed improvement after insulin treatment opens the door to therapeutic alternatives for children who are exposed to poorly controlled gestational diabetes, and who may benefit from more individualized treatments.
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影响因子：
3.7
作者：
Jose Ramos-Rodriguez, Juan;Ortiz, Oscar;Garcia-Alloza, Monica
通讯作者：
Garcia-Alloza, Monica
影响因子：
4.7
作者：
Aggarwal, Aanchal;Khera, Alka;Sandhir, Rajat
通讯作者：
Sandhir, Rajat
糖尿病控制不善的APP/PS1小鼠中自发性中心出血和认知障碍增加。
影响因子：
5.1
作者：
Ramos-Rodriguez JJ;Infante-Garcia C;Galindo-Gonzalez L;Garcia-Molina Y;Lechuga-Sancho A;Garcia-Alloza M
通讯作者：
Garcia-Alloza M
影响因子：
16.2
作者：
Anna, Vibeke;van der Ploeg, Hidde P.;Cheung, N. Wah;Huxley, Rachel R.;Bauman, Adrian E.
通讯作者：
Bauman, Adrian E.
DOI：
10.1152/ajpendo.00500.2011
发表时间：
2012-06-01
影响因子：
5.1
作者：
Jimenez-Palomares, Margarita;Jose Ramos-Rodriguez, Juan;Cozar-Castellano, Irene
通讯作者：
Cozar-Castellano, Irene