Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America.
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America.
PLoS One. 2023 Oct 18;18(10):e0292952. doi: 10.1371/journal.pone.0292952. eCollection 2023.
This study aimed to improve our understanding of how the hypothalamus mediates the effects of prenatal and postnatal challenges on behavior and sensitivity to stimuli. A pig model of virally initiated maternal immune activation (MIA) was used to investigate potential interactions of the prenatal challenge both with sex and with postnatal nursing withdrawal. The hypothalami of 72 females and males were profiled for the effects of MIA and nursing withdrawal using RNA-sequencing. Significant differential expression (FDR-adjusted p value < 0.05) was detected in the profile of 222 genes. Genes involved in the Gene Ontology biological process of regulation of hormone levels tended to be over-expressed in individuals exposed to both challenges relative to individuals exposed to either one challenge, and most of these genes were over-expressed in MIA females relative to males across nursing levels. Differentially expressed genes included Fshb, Ttr, Agrp, Gata3, Foxa2, Tfap2b, Gh1, En2, Cga, Msx1, and Npy. The study also found that prenatal and postnatal challenges, as well as sex, impacted the regulation of neurotransmitter activity and immune effector processes in the hypothalamus. In particular, the olfactory transduction pathway genes were over-expressed in weaned MIA males, and several transcription factors were potentially found to target the differentially expressed genes. Overall, these results highlight how multiple environmental challenges can interact and affect the molecular mechanisms of the hypothalamus, including hormonal, immune response, and neurotransmitter processes.
本研究旨在增进我们对下丘脑如何介导产前和产后挑战对行为和对刺激敏感性的影响的理解。采用病毒引发的母体免疫激活（MIA）猪模型，研究了产前挑战与性别和产后哺乳中断的潜在相互作用。使用 RNA 测序对 72 只雌性和雄性猪的下丘脑进行 MIA 和哺乳中断的影响分析。在 222 个基因的图谱中检测到显著的差异表达（经 FDR 调整的 p 值 < 0.05）。涉及激素水平调节的基因本体生物学过程的基因在同时暴露于两种挑战的个体中倾向于表达过度，与仅暴露于一种挑战的个体相比，并且这些基因在 MIA 雌性中相对于雄性在所有哺乳水平下表达过度。差异表达的基因包括 Fshb、Ttr、Agrp、Gata3、Foxa2、Tfap2b、Gh1、En2、Cga、Msx1 和 Npy。该研究还发现，产前和产后挑战以及性别会影响下丘脑神经递质活性和免疫效应过程的调节。特别是，断奶的 MIA 雄性中嗅觉转导途径基因表达过度，并且可能发现了几种转录因子作为潜在的差异表达基因的靶点。总的来说，这些结果强调了多种环境挑战如何相互作用并影响下丘脑的分子机制，包括激素、免疫反应和神经递质过程。
