产前应激引起子鼠的抑郁样行为和HDACs的改变

Changes of HDACs and Depressive-like Behavior in the Prenatally Stressed Offspring

越来越多的研究发现产前应激(prenatal stress,PS)能引起子代大鼠的抑郁样行为。然而,其脑内潜在分子机制仍有许多不为人知。为了探讨PS对一月龄子代大鼠抑郁样行为及其脑内组蛋白去乙酰化酶(histone deacetylases,HDACs)的影响,本研究选用32只子代雄鼠为研究对象,以每组8只分为4组:对照组(control,C)、产前应激组(PS)、产前应激给丁酸钠(sodium butyrate,Na B)组(PS+Na B)和产前应激给生理盐水(normal saline,NS)组(PS+NS)。所有子鼠在生后第30天进行强迫游泳和高价十字迷宫的行为学检测,然后断头取脑,用RT-PCR检测海马、皮层中HDAC2和HDAC5的基因表达水平。结果表明:与对照组相比,PS子鼠抑郁样行为增加,并伴随着海马HDAC5的过表达,而皮层HDAC5表达没有明显改变;PS子鼠给与Na B腹腔注射后,抑郁样行为改善,海马HDAC5表达也明显降低。HDAC2在各组子鼠的海马和皮层中均没有明显差异。该文不仅揭示了PS通过诱导HDAC5的改变从而引起子鼠的抑郁样行为,同时也为抗抑郁症药物的研究提供新的理论依据和药物靶点。

Increasing evidence revealed that prenatal stress(PS) could induce depressive-like behavior in offspring.However, the underlying molecular pathogenesis in brain remains largely elusive. In order to explore the effect of PS on depressive-like behavior and HDACs in brain of 1-month-old offspring rats, in the present study, we employed 32 male SD offspring rats as the experimental materials, which were allocated to 4 groups(8 per group):C(control group), PS(prenatal stress), PS+Na B(prenatal stressv Na B) and PS+NS(prenatal stress+normal saline).All offspring rats for forced swimming test and elevated-plus maze on postnatal day 30, and then decapitated,prepared the hippocampus and cortex to measure the expression of HDAC2 and HDAC5 m RNA with RT-PCR.Results exhibited that the PS offspring showed higher depressive-like behavior compared to C group and accompanied overexpression of HDAC5 in hippocampus, but no difference in cortex; After administrated with Na B, the depressive-like behavior were improved and decreased the overexpression of HDAC5 in PS offspring rats. We also didn't find significant differences in four groups about HDAC2 in hippocampus and cortex. In this research, not only we suggested that PS caused depressive-like behavior in offspring rats via changed HDAC5, also provide new theoretical basis and drug targets for excavating antidepressant.