Wang Bo, Li Ming
College of Biological and Environmental Engineering/Key Laboratory of Natural Product Development and Anticancer Innovative Drug Research in Qinling, Xi'an University, Xi'an 710065, China.
Department of Psychology, Nanjing University, Nanjing 210023, China.
Brain Behav Immun Integr. 2025 Jan;9. doi: 10.1016/j.bbii.2024.100098. Epub 2024 Dec 11.
This exploratory study investigated the neural substrate underlying the effect of gestational stress on rat maternal behavior. We tested the hypothesis that the lateral habenula (LHb)-centered neural circuitry (e.g., raphe, ventral tegmental area, nucleus accumbens, etc.) mediates the maternal disruptive effect of gestational stress. Pregnant Sprague-Dawley rats were subjected to daily 30-min restraining stress from approximately gestation day (GD) 5 to 21, white noise from GD 5 to 12 and mild foot shock from GD 13 to 21. Maternal behavior in the home cage and pup retrieval on an elevated plus maze (EPM) were observed during the first postpartum week. The gestational stress reduced body weight gain of stressed females, and reduced time that they spent outside of the nest, a sign of increased maternal anxiety and hypervigilant parenting style. On the open arms of EPM, the stressed dams showed higher frequently sniffing pups than non-stressed ones. Testing with pups (pup exposure) on the EPM decreased c-Fos expression in the LHb in the non-stressed control dams, but it increased c-Fos expression in the dorsal and medial raphe regions of the control dams. Gestational stress reduced this pup effect in all three regions, implying that gestational stress attenuated the ability of pup exposure to activate the maternally relevant brain regions. Our findings indicate that gestational stress may act upon the LHb (as a putative center that mediates negative emotion) and its downstream projection sites (i.e., dorsal and median raphe) to compromise the quality of maternal care.
这项探索性研究调查了孕期应激影响大鼠母性行为的神经基础。我们检验了以下假设：以外侧缰核（LHb）为中心的神经回路（如中缝核、腹侧被盖区、伏隔核等）介导了孕期应激对母性行为的破坏作用。将怀孕的斯普拉格-道利大鼠从大约妊娠第5天至21天每天施加30分钟的束缚应激，从妊娠第5天至12天施加白噪声，从妊娠第13天至21天施加轻度足部电击。在产后第一周观察母鼠在笼内的行为以及在高架十字迷宫（EPM）上的幼崽找回行为。孕期应激降低了受应激母鼠的体重增加，并减少了它们在巢外的时间，这是母性焦虑增加和过度警觉育儿方式的一个迹象。在EPM的开放臂上，受应激的母鼠比未受应激的母鼠更频繁地嗅闻幼崽。在EPM上用幼崽进行测试（幼崽暴露）可降低未受应激对照母鼠LHb中的c-Fos表达，但会增加对照母鼠中缝背侧和中缝内侧区域的c-Fos表达。孕期应激在所有这三个区域均减弱了这种幼崽效应，这意味着孕期应激削弱了幼崽暴露激活与母性相关脑区的能力。我们的研究结果表明，孕期应激可能作用于LHb（作为一个假定的介导负面情绪的中心）及其下游投射部位（即中缝背侧和中缝正中），从而损害母性照料的质量。
