RT journal article
T1 Intranasal insulin reverts central pathology and cognitive impairment in diabetic mother offspring
A1 Ramos Rodríguez, Juan José
A1 Sánchez Sotano, Daniel
A1 Infante-Garcia, Carmen
A1 Lubián López, Simón Pedro
A1 García Alloza, Mónica
A2 BiomedicinaBiotecnología y Salud Pública
A2 Materno-Infantil y Radiología
K1 Diabetes
K1 Offspring
K1 Insulin
K1 Tau
K1 Haemorrhage
K1 Inflammation
AB Background: 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. Methods: 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. Results: 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. Conclusions: 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.
PB BioMed Central Ltd.
SN 1750-1326
YR 2017
FD 2017
LK http://hdl.handle.net/10498/33867
UL http://hdl.handle.net/10498/33867
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 10-nov-2026