Histone Acetylation Modification Of 5-HT1A And BDNF In Depressive-like Behavior Of The Prenatally Stressed Offspring

ObjectiveThe pathogenesis of depression is associated with a series of genetic, neurotransmitter disturbance, hormone dysregulation and diverse psychosocial factors, which resulted 5-HT deficiency is one of the broadly acknowledged mechanisms. Becuase that brain 5-HT1A receptor can be regards as an important mediator in the development of stress adaptation, which possessing protective effects against emotional disorders produced by stress stimuli. meanwhile,5-HTT by 5-HT uptake controlling 5-HT,5-HT and BDNF are involved in disorder of pathophysiology, so we think it is important to research 5-HTlA、5-HTT and BDNF for depression.Previous studies have demonstrated that histone acetylation modification is involved in the stress-related psychiatric disorders including depression. However, these researches mainly focused on the regulation of histone acetylation in depressed adult responses to stress, few studies have explored the effects of PS on post-translational histone modifications directly in the PS offspring. To investigate whether PS changed HDAC4 expression, furthermore, effected the level of histone acetylation at promoter region of 5-HT1A、5-HTT and BDNF and contributed to depressive-like behavior of PS offspring, we established the prenatal stress model and examined the level of histone acetylation at promoter region and genes expression of 5-HT1A、 5-HTT and BDNF in the hippocampus.Methods:The offspring male rats were allocated to 4 groups (10 per group):①C (Control group), ②PS (prenatal stress), ③PS+NaB (prenatal stress+NaB), ④PS+NS (prenatal stress+saline). The PS+NS group received once a day administration of saline and the PS+NaB group with NaB on postnatal day 23 for seven days continuously, the others feed normally. All offspring rats for behavioral test on postnatal day 30 and then decapitated hippocampus to measure acetylated histone of 5-HT1A、5-HTT and BDNF in promoters with CHIP, RT-PCR were used to determine the expression of HDAC4、5-HT1A、5-HTT and BDNF.Results:1. PS group rats showed lower sucrose preference for in sucrose preference test than C group; In the EPM, PS group showed lower level of percentage of open-arm entries and open-arm time compared with C group; PS group showed more the immobility time in FST than C group.2. After NaB treatment, the depressive-like behavior alleviated in PS group.3. The level of histone acetylation at promoter region for 5-HT1A and BDNF lower in PS group than C group.4. PS significantly decreased the levels of total 5-HT1A receptor and BDNF mRNA, but not 5-HTT.5. NaB prevented the changes of histone acetylation at promoter region of 5-HT1A and BDNF.Conclusion:1. PS induced offspring rats depressive-like behavior.2. PS increased the expression of HDAC4 mRNA, furthermore, down-regulated the level of histone acetylation at promoter region of 5-HT1A and BDNF.3. Decresed histone acetylation at promoter of 5-HT1A and BDNF depressed the expression of 5-HT1A and BDNF.4. NaB partially reversed the level of histone acetylation at promoter region and the expression of 5-HT1A and BDNF induced by PS via depressed the expression of HDAC4, furthermore, improved the depressive-like behavior of PS group rats.