Prenatal stress increased Snk Polo-like kinase 2, SCF β-TrCP ubiquitin ligase and ubiquitination of SPAR in the hippocampus of the offspring at adulthood
Prenatal stress increased Snk Polo-like kinase 2, SCF β-TrCP ubiquitin ligase and ubiquitination of SPAR in the hippocampus of the offspring at adulthood
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DOI：
10.1016/j.ijdevneu.2013.06.011
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发表时间：
2013-11-01
影响因子：
1.8
通讯作者：
Surakul, Pornprom
中科院分区：
文献类型：
--
作者：
Chutabhakdikul, Naunchan;Surakul, Pornprom
在胎儿发育期间暴露于过量的糖皮质激素有助于以后的生活精神病理学。出生前应激可导致大鼠海马树突棘密度降低，LTP受损，但其调控机制尚不清楚，谷氨酸受体位于突触后致密区。PSD-95是一种突触后支架蛋白，在突触成熟和调节突触强度和可塑性中起作用。PSD-95与其他蛋白质相互作用，形成促进树突棘形成的蛋白质网络。本研究探讨了产前应激对海马NMDA受体支架蛋白水平的影响，以解释产前应激如何改变幼鼠脑中NMDA受体的数量。将妊娠大鼠随机分配到产前应激组（PS）或对照组（C）。在GD 14-21期间，将PS组中的妊娠大鼠束缚在有机玻璃束缚器中，每天4小时。对照组大鼠在妊娠期间不受干扰。测量了后代海马中PSD-95、SPAR、NR 2A和NR 2B的含量，以及Snk Polo样激酶2和SCF β-TrCP遍在蛋白连接酶的水平。结果表明，产前应激诱导大鼠仔鼠海马中NR 2B和NR 2A亚基的量减少，与P40和P60时PSD-95和SPAR的减少平行。此外，产前应激增加Snk和p-TrCP在海马的大鼠幼崽，和时间相关的减少SPAR和PSD-95。产前应激也诱导成年期大鼠海马中泛素化SPAR水平显著增加。结果提示，SPAR通过UPS系统降解可能导致成年大鼠海马PSD-95和NMDA受体亚单位的丢失。总之，目前的工作表明，发育中的大脑受到糖皮质激素的严重影响，特别是在产前和产后早期，这可能对大脑发育产生长期影响。此外，参与的UPS系统在产前压力模型，导致了更好地了解产前压力的影响以后的生活。(C)2013 ISDN。由爱思唯尔有限公司出版。保留所有权利。
Exposure to excessive glucocorticoids during fetal development period contributes to later life psychopathology. Prenatal stress decreases dendritic spine density and impair LTP in the hippocampus of rat pups, however, the mechanisms regulating these changes are still unclear.Glutamate receptors are localized in the postsynaptic density. PSD-95 is a postsynaptic scaffolding protein that plays a role in synaptic maturation and regulation of the synaptic strength and plasticity. PSD-95 interacts with other proteins to form the protein networks that promote dendritic spine formation. The present study investigated the effect of prenatal stress on the levels of scaffolding proteins of NMDA receptor in the hippocampus in order to explain how prenatal stress alters the amount of NMDA receptor in the pups' brain. Pregnant rats were randomly assigned to either the prenatal stress (PS) or the control group (C). The pregnant rats in the PS group were restrained in a plexiglas restrainer for 4 h/day during the GD 14-21. Control rats were left undisturbed for the duration of their pregnancies. The amount of PSD-95, SPAR, NR2A and NR2B, as well as the levels of Snk Polo-like kinase 2 and the SCF beta-TrCP ubiquitin ligase were measured in the hippocampus of the offspring. The results show that prenatal stress induces a reduction in the amount of NR2B and NR2A subunits in the hippocampus of rat pups, parallel to the decrease in PSD-95 and SPAR at P40 and P60. Moreover, prenatal stress increases Snk and p-TrCP in the hippocampus of rat pups, and the timing correlates with the decrease of SPAR and PSD-95. Prenatal stress also induces a significantly increases in the level of ubiquitinated SPAR in the hippocampus of rat pups at adulthood. The results suggest that degradation of SPAR via UPS system may contribute to the loss of PSD-95 and NMDA receptor subunits in the hippocampus of rat pups at adulthood. In conclusion, the present work demonstrates that the developing brain is critically influenced by glucocorticoids, especially during pre- and early postnatal period, which can have long-term effects on brain development. In addition, an involvement of the UPS system in the prenatal stress model has led to a greater understanding of the effects of prenatal stress later on in life. (C) 2013 ISDN. Published by Elsevier Ltd. All rights reserved.