Department of Animal Physiology, Complutense University of Madrid, Spain.
Acta Physiol (Oxf). 2009 Dec;197(4):333-40. doi: 10.1111/j.1748-1716.2009.02027.x. Epub 2009 Jul 25.
This study examines the effect of reducing the corticosterone levels of gestating rat dams on the postnatal development and maturation of monoaminergic systems in their offspring's brains.
Metyrapone, an inhibitor of CORT synthesis, was administered to pregnant rats from E0 to E17 of gestation. Monoamine concentrations were determined in male and female offspring at postnatal days (PN) 23 and 90 in the hippocampus, hypothalamus and striatum.
Reducing maternal corticosterone (mCORT) during gestation led to alterations in dopamine and serotonin levels in all three brain areas studied at PN 23. Alterations persisted until at least PN 90 in the serotonergic systems; the dopamine content of the hippocampus also remained modified. Reduced mCORT during gestation also led to alterations in the development and maturation of the hypothalamic noradrenergic systems. Sexually dimorphic responses were observed in all these monoaminergic systems at different times.
These results suggest that while they are still developing, brain monoaminergic systems are particularly sensitive to epigenetic influences. An adequate foetal level of CORT is required for the normal ontogeny of brain monoaminergic systems. The present data also provide that during the critical period of brain development, maternal CORT plays an important role in the sexual differentiation of monoaminergic systems, with particular influence on brain serotonergic neurones.
本研究探讨了降低孕鼠皮质酮（CORT）水平对其后代大脑中单胺能系统出生后发育和成熟的影响。
从妊娠 E0 到 E17 ，给予孕鼠米他孕酮（一种 CORT 合成抑制剂）。在出生后第 23 天（PN23）和第 90 天（PN90），检测雄性和雌性后代海马体、下丘脑和纹状体中单胺类物质的浓度。
孕期降低母源性皮质酮（mCORT）导致所有三个研究脑区的多巴胺和 5-羟色胺水平在 PN23 时发生改变。这种改变至少持续到 PN90；海马体的多巴胺含量也保持改变。孕期降低 mCORT 还导致下丘脑去甲肾上腺素能系统的发育和成熟发生改变。在所有这些单胺能系统中，都在不同时间观察到性别二态性反应。
这些结果表明，大脑单胺能系统在发育过程中特别容易受到表观遗传的影响。胎儿期需要足够的 CORT 水平才能使大脑单胺能系统正常发育。本研究数据还表明，在大脑发育的关键时期，母源性 CORT 在单胺能系统的性别分化中发挥重要作用，对脑内 5-羟色胺神经元有特殊影响。
