Ryu Min-Ok, Jung Ji-Youl, Suh Han Na, Lee Chung-Young, Kim Myung-Chul, Oh Ji Young, Song Woo-Jin, Ahn Changhwan, Yang Yeseul, Choi Gee Euhn
Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Korea.
College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, Jeju, 63243, Korea.
Cell Mol Neurobiol. 2024 Dec 23;45(1):7. doi: 10.1007/s10571-024-01525-x.
Chronic exposure to prenatal stress can impair neurogenesis and lead to irreversible cognitive and neuropsychiatric abnormalities in offspring. The retina is part of the nervous system; however, the impacts of prenatal stress on retinal neurogenesis and visual function remain unclear. This study examined how elevated prenatal glucocorticoid levels differentially affect retinal development in the offspring of pregnant mice exposed to chronic unpredictable mild stress (CUMS). Offspring were classified into control, stress-resilient, and stress-susceptible groups based on behavioral tests assessing spatial memory and depression-like behaviors. The stress-susceptible group exhibited significantly altered synaptogenesis, reduced ganglion cell development, decreased retinal thickness, and visiual impairment. These mice also showed a pervasive transformation of retinal astrocytes into a proinflammatory A1-like reactive state, evidenced by increased GFAP and decreased STAT3 expression levels. This astrocyte phenotype shift coincided with disruptions in neurogenesis and synaptic formation. Furthermore, prenatal exposure to exogenous corticosterone confirmed that the effects of prenatal stress are mediated by glucocorticoid-induced retinal neurodegeneration. Our findings suggest that elevated prenatal glucocorticoid levels trigger a series of neurodevelopmental disturbances leading to retinal neurodegeneration and vision impairment. This research highlights the impact of prenatal stress on retinal development and visual health, suggesting new avenues for understanding and potentially mitigating the negative effects of early-life stress on neurodevelopment.
长期暴露于产前应激会损害神经发生，并导致后代出现不可逆的认知和神经精神异常。视网膜是神经系统的一部分；然而，产前应激对视网膜神经发生和视觉功能的影响仍不清楚。本研究考察了孕期暴露于慢性不可预测轻度应激（CUMS）的孕鼠后代中，产前糖皮质激素水平升高如何差异地影响视网膜发育。根据评估空间记忆和抑郁样行为的行为测试，将后代分为对照组、应激耐受组和应激易感组。应激易感组表现出明显改变的突触发生、神经节细胞发育减少、视网膜厚度降低和视觉障碍。这些小鼠还表现出视网膜星形胶质细胞广泛转变为促炎的A1样反应状态，表现为GFAP增加和STAT3表达水平降低。这种星形胶质细胞表型转变与神经发生和突触形成的破坏同时发生。此外，产前暴露于外源性皮质酮证实，产前应激的影响是由糖皮质激素诱导的视网膜神经变性介导的。我们的研究结果表明，产前糖皮质激素水平升高会引发一系列神经发育障碍，导致视网膜神经变性和视力损害。这项研究突出了产前应激对视网膜发育和视觉健康的影响，为理解并潜在减轻早期生活应激对神经发育的负面影响提供了新途径。
