Department of Human Physiology, University of KwaZulu-Natal, Durban, 4000, South Africa.
Metab Brain Dis. 2009 Dec;24(4):525-39. doi: 10.1007/s11011-009-9161-6. Epub 2009 Oct 21.
Prenatal stress has been associated with increased vulnerability to psychiatric disturbances including schizophrenia, depression, attention-deficit hyperactivity disorder and autism. Elevated maternal circulating stress hormones alter development of neural circuits in the fetal brain and cause long-term changes in behaviour. The aim of the present study was to investigate whether mild prenatal stress increases the vulnerability of dopamine neurons in adulthood. A low dose of 6-hydroxydopamine (6-OHDA, 5 microg/4 microl saline) was unilaterally infused into the medial forebrain bundle of nerve fibres in the rat brain in order to create a partial lesion of dopamine neurons which was sufficient to cause subtle behavioural deficits associated with early onset of Parkinson's disease without complete destruction of dopamine neurons. Voluntary exercise appeared to have a neuroprotective effect resulting in an improvement in motor control and decreased asymmetry in the use of left and right forelimbs to explore a novel environment as well as decreased asymmetry of tyrosine hydroxylase-positive cells in the substantia nigra pars compacta and decreased dopamine cell loss in 6-OHDA-lesioned rats. Prenatal stress appeared to enhance the toxic effect of 6-OHDA possibly by reducing the compensatory adaptations to exercise.
产前应激与精神障碍易感性增加有关,包括精神分裂症、抑郁症、注意力缺陷多动障碍和自闭症。母体循环应激激素水平升高会改变胎儿大脑神经回路的发育,并导致行为的长期变化。本研究旨在探讨轻度产前应激是否会增加成年多巴胺神经元的易损性。将低剂量的 6-羟多巴胺(6-OHDA,5 微克/4 微升生理盐水)单侧注入大鼠脑内的神经纤维中脑束,以造成多巴胺神经元的部分损伤,足以导致与帕金森病早期发病相关的微妙行为缺陷,而不会完全破坏多巴胺神经元。自愿运动似乎具有神经保护作用,导致运动控制改善,探索新环境时左右前肢的使用不对称性降低,以及黑质致密部酪氨酸羟化酶阳性细胞的不对称性降低和 6-OHDA 损伤大鼠的多巴胺神经元丢失减少。产前应激似乎通过降低对运动的代偿适应来增强 6-OHDA 的毒性作用。