Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, United States.
Department of Psychiatry, Oregon Health & Science University, Portland, Oregon, United States.
J Neurophysiol. 2024 Feb 1;131(2):241-260. doi: 10.1152/jn.00213.2023. Epub 2024 Jan 10.
Perinatal exposure to a high-fat, high-sugar Western-style diet (WSD) is associated with altered neural circuitry in the melanocortin system. This association may have an underlying inflammatory component, as consumption of a WSD during pregnancy can lead to an elevated inflammatory environment. Our group previously demonstrated that prenatal WSD exposure was associated with increased markers of inflammation in the placenta and fetal hypothalamus in Japanese macaques. In this follow-up study, we sought to determine whether this heightened inflammatory state persisted into the postnatal period, as prenatal exposure to inflammation has been shown to reprogram offspring immune function and long-term neuroinflammation would present a potential means for prolonged disruptions to microglia-mediated neuronal circuit formation. Neuroinflammation was approximated in 1-yr-old offspring by counting resident microglia and peripherally derived macrophages in the region of the hypothalamus examined in the fetal study, the arcuate nucleus (ARC). Microglia and macrophages were immunofluorescently stained with their shared marker, ionized calcium-binding adapter molecule 1 (Iba1), and quantified in 11 regions along the rostral-caudal axis of the ARC. A mixed-effects model revealed main effects of perinatal diet ( = 0.011) and spatial location ( = 0.003) on Iba1-stained cell count. Perinatal WSD exposure was associated with a slight decrease in the number of Iba1-stained cells, and cells were more densely located in the center of the ARC. These findings suggest that the heightened inflammatory state experienced in utero does not persist postnatally. This inflammatory response trajectory could have important implications for understanding how neurodevelopmental disorders progress. Prenatal Western-style diet exposure is associated with increased microglial activity in utero. However, we found a potentially neuroprotective reduction in microglia count during early postnatal development. This trajectory could inform the timing of disruptions to microglia-mediated neuronal circuit formation. Additionally, this is the first study in juvenile macaques to characterize the distribution of microglia along the rostral-caudal axis of the arcuate nucleus of the hypothalamus. Nearby neuronal populations may be greater targets during inflammatory insults.
围产期暴露于高脂肪、高糖的西式饮食（WSD）与黑素皮质素系统中的神经回路改变有关。这种关联可能具有潜在的炎症成分，因为怀孕期间摄入 WSD 会导致炎症环境升高。我们的研究小组之前曾表明，产前 WSD 暴露与日本猕猴胎盘中炎症标志物的增加以及胎儿下丘脑中的炎症标志物增加有关。在这项后续研究中，我们试图确定这种加剧的炎症状态是否会持续到产后时期，因为产前暴露于炎症已被证明会重新编程后代的免疫功能，而长期的神经炎症可能是长期破坏小胶质细胞介导的神经元回路形成的潜在手段。通过对胎儿研究中检查的下丘脑区域即弓状核（ARC）中的常驻小胶质细胞和外周衍生的巨噬细胞进行计数，来近似 1 岁龄后代的神经炎症。小胶质细胞和巨噬细胞用其共同标志物离子钙结合接头分子 1（Iba1）进行免疫荧光染色，并在 ARC 的头侧-尾侧轴上的 11 个区域进行定量。混合效应模型显示围产期饮食（ = 0.011）和空间位置（ = 0.003）对 Iba1 染色细胞计数有主要影响。围产期 WSD 暴露与 Iba1 染色细胞数量略有减少有关，并且细胞在 ARC 的中心更密集。这些发现表明，宫内经历的高度炎症状态不会持续到产后。这种炎症反应轨迹对于理解神经发育障碍的进展具有重要意义。产前西式饮食暴露与宫内小胶质细胞活性增加有关。然而，我们发现，在早期产后发育过程中小胶质细胞数量减少，这可能具有神经保护作用。这种轨迹可以为小胶质细胞介导的神经元回路形成的中断提供时间线索。此外，这是在幼年猕猴中描述下丘脑弓状核头侧-尾侧轴上小胶质细胞分布的第一项研究。在炎症损伤时，附近的神经元群体可能是更大的靶标。
