Strackx Eveline, Jellema Reint K, Rieke Rebecca, Gussenhoven Ruth, Vles Johan S H, Kramer Boris W, Gavilanes Antonio W D
School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University and European Graduate, School of Neuroscience (EURON), Universiteitssingel 50, Room 1.152, 6229 MD Maastricht, Netherlands ; Department of Pediatrics-Neonatology, Maastricht University Medical Center (MUMC), Postbus 5800, 6202 AZ Maastricht, Netherlands.
School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University and European Graduate, School of Neuroscience (EURON), Universiteitssingel 50, Room 1.152, 6229 MD Maastricht, Netherlands.
Biomed Res Int. 2015;2015:276029. doi: 10.1155/2015/276029. Epub 2015 Aug 31.
Chorioamnionitis has been associated with increased risk for fetal brain damage. Although, it is now accepted that synaptic dysfunction might be responsible for functional deficits, synaptic densities/numbers after a fetal inflammatory challenge have not been studied in different regions yet. Therefore, we tested in this study the hypothesis that LPS-induced chorioamnionitis caused profound changes in synaptic densities in different regions of the fetal sheep brain.
Chorioamnionitis was induced by a 10 mg intra-amniotic LPS injection at two different exposure intervals. The fetal brain was studied at 125 days of gestation (term = 150 days) either 2 (LPS2D group) or 14 days (LPS14D group) after LPS or saline injection (control group). Synaptophysin immunohistochemistry was used to quantify the presynaptic density in layers 2-3 and 5-6 of the motor cortex, somatosensory cortex, entorhinal cortex, and piriforme cortex, in the nucleus caudatus and putamen and in CA1/2, CA3, and dentate gyrus of the hippocampus.
There was a significant reduction in presynaptic bouton densities in layers 2-3 and 5-6 of the motor cortex and in layers 2-3 of the entorhinal and the somatosensory cortex, in the nucleus caudate and putamen and the CA1/2 and CA3 of the hippocampus in the LPS2D compared to control animals. Only in the motor cortex and putamen, the presynaptic density was significantly decreased in the LPS14 D compared to the control group. No changes were found in the dentate gyrus of the hippocampus and the piriforme cortex.
We demonstrated that LPS-induced chorioamnionitis caused a decreased density in presynaptic boutons in different areas in the fetal brain. These synaptic changes seemed to be region-specific, with some regions being more affected than others, and seemed to be transient in some regions.
绒毛膜羊膜炎与胎儿脑损伤风险增加有关。尽管目前人们认为突触功能障碍可能是功能缺陷的原因，但胎儿炎症刺激后的突触密度/数量在不同区域尚未得到研究。因此，我们在本研究中检验了以下假设：脂多糖（LPS）诱导的绒毛膜羊膜炎会导致胎羊脑不同区域的突触密度发生深刻变化。
通过在羊膜腔内注射10毫克LPS，以两种不同的暴露间隔诱导绒毛膜羊膜炎。在妊娠125天（足月为150天）时，对LPS或生理盐水注射后2天（LPS2D组）或14天（LPS14D组）的胎脑进行研究（对照组）。采用突触素免疫组织化学法对运动皮层、体感皮层、内嗅皮层和梨状皮层的第2 - 3层和第5 - 6层、尾状核和壳核以及海马体的CA1/2、CA3和齿状回中的突触前密度进行量化。
与对照动物相比，LPS2D组运动皮层第2 - 3层和第5 - 6层、内嗅皮层和体感皮层第2 - 层以及尾状核、壳核、海马体的CA1/2和CA3中的突触前终扣密度显著降低。与对照组相比，仅在运动皮层和壳核中，LPS14D组的突触前密度显著降低。在海马体的齿状回和梨状皮层中未发现变化。
我们证明，LPS诱导的绒毛膜羊膜炎导致胎脑不同区域的突触前终扣密度降低。这些突触变化似乎具有区域特异性，某些区域比其他区域受影响更大，并且在某些区域似乎是短暂的。
