Section of Psychiatry, Laboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Department of Neuroscience, Reproductive Sciences and Dentistry, University Medical School of Naples "Federico II", Naples, Italy; Department of Translational Medical Sciences, University of Naples "Federico II", Via S. Pansini 5, 80131 Naples, Italy.
Section of Psychiatry, Laboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Department of Neuroscience, Reproductive Sciences and Dentistry, University Medical School of Naples "Federico II", Naples, Italy.
Prog Neuropsychopharmacol Biol Psychiatry. 2024 Jul 13;133:111032. doi: 10.1016/j.pnpbp.2024.111032. Epub 2024 May 16.
Early life stress may induce synaptic changes within brain regions associated with behavioral disorders. Here, we investigated glutamatergic functional connectivity by a postsynaptic density immediate-early gene-based network analysis. Pregnant female Sprague-Dawley rats were randomly divided into two experimental groups: one exposed to stress sessions and the other serving as a stress-free control group. Homer1 expression was evaluated by in situ hybridization technique in eighty-eight brain regions of interest of male rat offspring. Differences between the perinatal stress exposed group (PRS) (n = 5) and the control group (CTR) (n = 5) were assessed by performing the Student's t-test via SPSS 28.0.1.0 with Bonferroni correction. Additionally, all possible pairwise Spearman's correlations were computed as well as correlation matrices and networks for each experimental group were generated via RStudio and Cytoscape. Perinatal stress exposure was associated with Homer1a reduction in several cortical, thalamic, and striatal regions. Furthermore, it was found to affect functional connectivity between: the lateral septal nucleus, the central medial thalamic nucleus, the anterior part of the paraventricular thalamic nucleus, and both retrosplenial granular b cortex and hippocampal regions; the orbitofrontal cortex, amygdaloid nuclei, and hippocampal regions; and lastly, among regions involved in limbic system. Finally, the PRS networks showed a significant reduction in multiple connections for the ventrolateral part of the anteroventral thalamic nucleus after perinatal stress exposure, as well as a decrease in the centrality of ventral anterior thalamic and amygdaloid nuclei suggestive of putative reduced cortical control over these regions. Within the present preclinical setting, perinatal stress exposure is a modifier of glutamatergic early gene-based functional connectivity in neuronal circuits involved in behaviors relevant to model neurodevelopmental disorders.
早期生活压力可能会导致与行为障碍相关的大脑区域的突触变化。在这里，我们通过基于突触后密度即刻早期基因的网络分析研究了谷氨酸能功能连接。将怀孕的 Sprague-Dawley 雌性大鼠随机分为两组：一组暴露于应激组，另一组作为无应激对照组。通过原位杂交技术评估雄性大鼠后代 88 个感兴趣脑区的 Homer1 表达。通过 SPSS 28.0.1.0 中的学生 t 检验评估围产期应激暴露组 (PRS) (n=5) 和对照组 (CTR) (n=5) 之间的差异，并进行 Bonferroni 校正。此外，还计算了所有可能的成对 Spearman 相关系数，并通过 RStudio 和 Cytoscape 生成了每个实验组的相关矩阵和网络。围产期应激暴露与皮质、丘脑和纹状体的几个区域 Homer1a 减少有关。此外，它还影响了：外侧隔核、中央内侧丘脑核、室旁丘脑前核，以及 retrosplenial 颗粒 b 皮质和海马区之间的功能连接；眶额皮质、杏仁核和海马区；最后，在参与边缘系统的区域之间。最后，PRS 网络显示，在围产期应激暴露后，anteroventral 丘脑腹侧下部分的多个连接显著减少，腹侧前丘脑和杏仁核的中心性降低，提示皮质对这些区域的控制可能降低。在目前的临床前环境中，围产期应激暴露是参与与神经发育障碍相关行为的神经元回路中谷氨酸能早期基因功能连接的修饰因子。
