Synaptic structure and alterations in the hippocampus in neonatal rats exposed to lipopolysaccharide
Synaptic structure and alterations in the hippocampus in neonatal rats exposed to lipopolysaccharide
复制标题
脂多糖暴露的新生大鼠海马突触结构和变化
DOI：
10.1016/j.neulet.2019.134364
复制
发表时间：
2019-09-14
影响因子：
2.5
通讯作者：
Deng, Yiyu
中科院分区：
文献类型：
--
作者：
Lin, Lanfen;Chen, Xuan;Deng, Yiyu
突触结构的完整性在学习和记忆中起着关键作用。以往的研究表明，败血症新生儿在以后的生活中存在认知功能障碍。本研究采用腹腔注射脂多糖（LPS）建立脓毒症大鼠模型，观察脓毒症对大鼠海马突触的影响。脓毒症组海马突触体蛋白（Syn）、25 kD突触体相关蛋白（SNAP-25）和N-甲基-d-天冬氨酸受体（NMDAR）的表达明显减少。与此相一致，LPS给药后28 d，海马CA 1区锥体神经元相关的树突棘数量减少。此外，突触和突触囊泡的数量减少，并出现肿胀。海马CA 1、CA 3区神经元数在注射LPS后14、28 d无明显变化。LPS注射后1-3d，IL-1 β、IL-1受体1、IL-6、TNF-α和诱导型一氧化氮合酶（iNOS）的表达上调。在活化的小胶质细胞中特异性检测到IL-1 β表达。LPS处理组大鼠血浆皮质酮（CORT）浓度升高，海马糖皮质激素受体（GR）表达降低。我们的结论是，LPS注射新生大鼠可导致海马突触破坏，这可能是由于促炎细胞因子（例如，IL-1 β来源于活化的小胶质细胞。血浆CORT浓度升高和海马GR表达降低的意义进行了讨论。
Synaptic structure integrity plays a key role in learning and memory. Previous studies have shown that there is cognitive dysfunction in septic neonates in later life. In this study, intraperitoneal injection of lipopolysaccharide (LPS) in the developing rats was used as a sepsis model to determine whether hippocampal synapses would be affected. Expression of synaptophysin (Syn), synaptosomal associated protein of 25 kD (SNAP-25), and N-methyl d-aspartate receptor (NMDAR) in the hippocampus in septic brain were significantly reduced. Consistent with this, the number of dendritic spines associated with the pyramidal neurons in the CA1 region of hippocampus at 28d after LPS administration was decreased. Additionally, the number of synapse and synaptic vesicles were reduced and appeared swollen. The number of neurons in the CA1 and CA3 of hippocampus at 14, and 28d after LPS injection remained unchanged. Coupled with the above was upregulated expression of interleukin-1 beta (IL-1 beta), IL-1 receptor 1 (IL-R1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) at 1-3d after LPS injection. IL-1 beta expression was specifically detected in activated microglia. The plasma corticosterone (CORT) concentration in the LPS treatment rats was increased; but the glucocorticoid receptor (GR) expression in the hippocampus was decreased. We conclude that LPS injection in neonatal rats can cause synaptic disruption in the hippocampus which may be attributed to inflammatory response due to excess production of proinflammatory cytokines e.g., IL-1 beta derived from activated microglia. The significance of increased plasma CORT concentration and decreased GR expression in the hippocampus is discussed.