The effect of maternal obesity on neural stem cell proliferation in pre natal mice

autism;asd;maternal;obesity;inflammation;Ki67;amygdala;hippocampus;cerebellum;natal;mice;proliferation

Gibbs, Jordan ; Jasoni, Christine

University of Otago

关键词: autism;    asd;    maternal;    obesity;    inflammation;    Ki67;    amygdala;    hippocampus;    cerebellum;    natal;    mice;    proliferation;   

Others  :  https://ourarchive.otago.ac.nz/bitstream/10523/5890/1/GibbsJordanB2015BMedScHons.pdf

美国|英语

来源: Otago University Research Archive

【 摘 要 】

Autism Spectrum Disorder (ASD) is a complex neurological condition. It affects approximately 1 in 110 people world wide, with a 4:1 ratio of males to females affected. ASD presents with a wide range of psychological symptoms including deficits in speech, motor function and cognition. Interestingly, ASD first presents symptomatically in the first three years of life, sometimes even presenting as a regression in acquired skills, such as language. Research has shown a multitude of anatomical changes to the brain, creating a specific pathology seen in subjects with ASD. This includes overall changes to brain volume, with a lower volume at birth followed by an excessive overgrowth, and, consequently, excessive brain volume in the first few years of life. In addition to these findings, a set of regions in the brain have been repeatedly found to be associated with ASD, such as the amygdala, hippocampus and cerebellum. These findings suggest neural stem cells could be altered, leading to the changes seen in ASD, which are present right from birth.Due to the condition being psychiatric there is no way to identify ASD until behavioural symptoms appear. Consequently, there is no way to know what pre-natal ASD looks like, due to the lack of a biological marker.Though the origins of ASD are, as of yet, unknown, a wide variety of research has identified a number of associations that are potentially linked to ASD. One such association is maternal obesity, or obesity during pregnancy. This is associated with an increase in the risk for offspring to develop ASD. The aim of the present study was to test this hypothesis using immunohistochemistry. We analysed the effects of maternal obesity on neural stem proliferation in regions of the brain commonly associated with ASD.To examine this association, we used a mouse model of maternal obesity to generate prenatal offspring and compared them to control offspring undergoing gestation in a mother of normal weight. We used pups from late mouse gestation, GD15.5 and GD17.5, examined neural stem cell proliferation using immunohistochemistry to detect the cell proliferation marker Ki67. This was completed in 3 core areas associated with ASD; the cerebellum, amygdala and hippocampus.We identified a significant decrease in the number of cells proliferating in the amygdala at both ages in pups from obese mothers. Furthermore, we found sex differences in these results, with decreases in cell proliferation greater in males. We did not see any significant differences in the hippocampus or cerebellum.These results show that maternal obesity alters neural stem cell proliferation in the amygdala. The postnatal consequences of this are currently unclear, however, as the early neonatal ASD brain is smaller than neurologically normal controls, it is tempting to suggest that these findings represent pre-natal ASD. Given that the size of the brain is altered in ASD, which suggests a defect in the proliferation of neural stem cells, combined with the fact that maternal obesity is a predisposing risk factor, we hypothesised that when the fetal brain undergoes development in an obese mother there will be alterations in neural stem cell proliferation in regions of the brain commonly associated with ASD