Viltart Odile, Mairesse Jérôme, Darnaudéry Muriel, Louvart Hélène, Vanbesien-Mailliot Christel, Catalani Assia, Maccari Stefania
Laboratory of Perinatal Stress, JE2365, University of Lille 1, 59655 Villeneuve d'Ascq, France.
Psychoneuroendocrinology. 2006 Jul;31(6):769-80. doi: 10.1016/j.psyneuen.2006.02.007. Epub 2006 Apr 18.
Prenatal stress (PS) durably influences responses of rats from birth throughout life by inducing deficits of the hypothalamo-pituitary-adrenal (HPA) axis feedback. The neuronal mechanisms sustaining such alterations are still unknown. The purpose of the present study was to determine whether in PS and control rats, the exposure to a mild stressor differentially induces Fos protein in hippocampus and locus coeruleus, brain areas involved in the feedback control of the HPA axis. Moreover, Fos protein expression was also evaluated in the hypothalamic paraventricular nucleus (PVN) that reflect the magnitude of the hormonal response to stress. Basal plasma corticosterone levels were not different between the groups, while, PS rats exhibited higher number of Fos-immunoreactive neurons than controls, in the hippocampus and locus coeruleus in basal condition. A higher basal expression of a marker of GABAergic synapses, the vGAT, was also observed in the hypothalamus of PS rats. Fifteen minutes after the end of the exposure to the open arm of the elevated plus-maze (mild stress) a similar increased plasma corticosterone levels was observed in both groups in parallel with an increased number of Fos-immunoreactive neurons in the PVN. Return to basal plasma corticosterone values was delayed only in the PS rats. On the contrary, after stress, no changes in Fos-immunoreactivity were observed in the hippocampus and locus coeruleus of PS rats compared to basal condition. After stress, only PS rats presented an elevation of the number of activated catecholaminergic neurons in the locus coeruleus. In conclusion, these results suggest for the first time that PS alters the neuronal activation of hippocampus and locus coeruleus implicated in the feedback mechanism of the HPA axis. These data give anatomical substrates to sustain the HPA axis hyperactivity classically described in PS rats after stress exposure.
产前应激（PS）通过诱导下丘脑-垂体-肾上腺（HPA）轴反馈缺陷，从出生起就持久地影响大鼠一生的反应。维持这种改变的神经元机制仍然未知。本研究的目的是确定在PS大鼠和对照大鼠中，暴露于轻度应激源是否会在海马体和蓝斑（参与HPA轴反馈控制的脑区）中差异诱导Fos蛋白。此外，还评估了下丘脑室旁核（PVN）中的Fos蛋白表达，该核反映了对应激激素反应的程度。两组之间的基础血浆皮质酮水平没有差异，而在基础状态下，PS大鼠海马体和蓝斑中Fos免疫反应性神经元的数量高于对照组。在PS大鼠的下丘脑还观察到GABA能突触标志物vGAT的基础表达较高。在高架十字迷宫开放臂暴露（轻度应激）结束15分钟后，两组血浆皮质酮水平均出现类似的升高，同时PVN中Fos免疫反应性神经元数量增加。仅PS大鼠的血浆皮质酮值恢复到基础水平有所延迟。相反，应激后，与基础状态相比，PS大鼠海马体和蓝斑中的Fos免疫反应性没有变化。应激后，只有PS大鼠蓝斑中活化的儿茶酚胺能神经元数量增加。总之，这些结果首次表明，PS改变了参与HPA轴反馈机制的海马体和蓝斑的神经元激活。这些数据为应激暴露后PS大鼠中经典描述的HPA轴亢进提供了解剖学基础。
