a Facultad de Ciencias Exactas, Físicas y Naturales , Universidad Nacional de Córdoba, Laboratorio de Fisiología Animal , Córdoba , Argentina.
b Facultad de Ciencias Médicas , Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Universidad Nacional de Córdoba Ciudad Universitaria , Córdoba , Argentina.
Int J Neurosci. 2019 Jun;129(6):540-550. doi: 10.1080/00207454.2018.1550398. Epub 2018 Dec 26.
The aim of this study was to analyze whether early maternal separation would result in long-term, persistent alterations in stress response in adulthood, altering mineralocorticoid receptor immunoreactivity (MR-ir) in the dorsal hippocampal areas [CA1, CA2, CA3 and dentate gyrus (DG)], paraventricular nucleus of the hypothalamus and medial and central nucleus of the amygdala, key structures involved in stress response regulation. We also analyzed whether chronic treatment with the antidepressant tianeptine reverses these possible changes.
Male Wistar rats were subjected to daily maternal separation for 4.5 h during 3 weeks or left undisturbed. As adults, they were exposed to chronic stress during 24 days or left undisturbed, and they were also daily treated with tianeptine (10 mg/kg i.p.) or isotonic solution.
In the CA2 and DG areas of the dorsal hippocampus, there was an increase in MR-ir in non-maternally separated and chronic stressed groups. Tianeptine raised MR-ir in the CA3. In the DG, control and maternally separated + chronic stress groups treated with tianeptine showed more MR-ir than their respective vehicle groups. In the paraventricular nucleus, tianeptine decreased MR-ir in non-separated groups, but not in maternally separated rats.
Our results support findings that early-life events induce long-term changes in stress response regulation, persistent into adulthood, which are manifested during challenges in later life, and that treatment with tianeptine, which tends to attenuate the hypothalamus-pituitary-adrenal axis dysregulation, depends on the individual experience of each rat.
本研究旨在分析早期母婴分离是否会导致成年后长期持续的应激反应改变，改变背侧海马区[CA1、CA2、CA3 和齿状回（DG）]、下丘脑室旁核以及杏仁核的内侧和中央核中糖皮质激素受体免疫反应（MR-ir），这些结构是应激反应调节的关键。我们还分析了慢性使用抗抑郁药噻奈普汀是否能逆转这些可能的变化。
雄性 Wistar 大鼠在 3 周内每天接受 4.5 小时的母婴分离，或不进行干预。成年后，它们接受 24 天的慢性应激或不进行干预，并每天接受噻奈普汀（10mg/kg 腹腔注射）或等渗溶液治疗。
在背侧海马的 CA2 和 DG 区，未分离的和慢性应激的大鼠的 MR-ir 增加。噻奈普汀增加了 CA3 的 MR-ir。在 DG 区，与各自的载体组相比，未分离组和母婴分离+慢性应激组用噻奈普汀治疗后显示出更多的 MR-ir。在室旁核中，噻奈普汀降低了未分离组的 MR-ir，但对母婴分离的大鼠没有影响。
我们的结果支持了以下观点，即早期生活事件会导致应激反应调节的长期变化，并持续到成年期，这些变化在以后的生活中会表现出来，而使用噻奈普汀治疗，这种治疗倾向于减轻下丘脑-垂体-肾上腺轴的失调，取决于每只大鼠的个体经历。
