Abstract
Prenatal exposure to synthetic glucocorticoids (sGCs) can increase the risk of affective disorders, such as depression, in adulthood. Given that exercise training can ameliorate depression and improve mitochondrial function, we sought to investigate whether exercise can ameliorate depression-like behavior induced by prenatal sGC exposure and mitochondria function contributes to that behavior. At first, we confirmed that prenatal dexamethasone (Dex) administration in late pregnancy resulted in depression-like behavior and elevated level of circulatory corticosterone in adult offspring. We then found that mRNA and protein expression of a number of mitochondrial genes was changed in the hippocampus of Dex offspring. Mitochondria in the hippocampus showed abnormal morphology, oxidative stress and dysfunction in Dex offspring. Intracerebroventricular (ICV) injection of the mitochondrial superoxide scavenger mitoTEMPO significantly alleviated depression-like behavior but did not significantly affect circulatory corticosterone level in Dex offspring. The adult Dex offspring treated with treadmill exercise starting at four-weeks of age showed ameliorated depressive-like behavior, improved mitochondrial morphology and function and reduced circulatory corticosterone level. Our data suggest mitochondria dysfunction contributes to depression-like behavior caused by prenatal sGC exposure. Intervention with exercise training in early life can reverse depression caused by prenatal Dex exposure, which is associated with improvement of mitochondrial function in the hippocampus.
Highlights
During late gestation, concentration of glucocorticoids (GCs) in the fetal circulation is exponentially increased, and this surge of GCs is critical for fetal organ development including the lungs and brain (Fowden and Forhead, 2009)
Using Q-PCR, we confirmed that uncoupling protein 3 (UCP3) expression was significantly upregulated whilst Slc25a21 and isocitrate dehydrogenase 2 (IDH2) expression was significantly downregulated in Dex offspring compared with control offspring (P < 0.01, Figures 2A–C)
Western blotting analysis showed that the protein level of UCP3 was significantly increased whilst the levels Slc25a21 and IDH2 were significantly decreased in Dex offspring compared with control offspring (P < 0.05, Figures 2D–F)
Summary
Concentration of glucocorticoids (GCs) in the fetal circulation is exponentially increased, and this surge of GCs is critical for fetal organ development including the lungs and brain (Fowden and Forhead, 2009). Mitochondia and Depression-Like Behavior of fetal organs and impede preterm delivery associated morbid symptoms, such as respiratory distress syndrome and intraventricular hemorrhage (Amiya et al, 2016). Many animal studies have demonstrated that repeated exposure to sGCs in late gestation leads to depression-like behavior and other modified behavior in adult offspring (Hiroi et al, 2016; Conti et al, 2017; Xu et al, 2018). A number of genes have been found to be associated with depression-like behavior (McCoy et al, 2017; Xu et al, 2018), the mechanisms underlying the prenatal GC programming of depression-like behavior remain largely unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
