Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Neuronal Networks Group, Instituto de Biologia Molecular e Celular da Universidade do Porto, Porto, Portugal; Departamento de Biomedicina, Faculdade de Medicina da Universidade do Porto, Porto, Portugal; Medibrain, Vila do Conde, Portugal; Brain Research Institute, Porto, Portugal.
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Neuronal Networks Group, Instituto de Biologia Molecular e Celular da Universidade do Porto, Porto, Portugal; Departamento de Biomedicina, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
Brain Res Bull. 2019 Oct;152:95-106. doi: 10.1016/j.brainresbull.2019.07.009. Epub 2019 Jul 10.
Studies in animal models of epilepsy revealed compromised serotonin (5-HT) transmission between the raphe nuclei and the brain limbic system. The goal of the present study was to evaluate the effects of epilepsy on the structural integrity of the dorsal (DR) and median (MnR) raphe nuclei and on the morphology of serotonergic fiber terminals in the dentate gyrus (DG), infralimbic cortex (IL) and medial septum (MS). The study was performed in adult Wistar rats using the kainate (9.5 mg/kg) status epilepticus (SE) model. Four months post-SE, the brainstem sections of the animals were immunostained for 5-HT, whereas the forebrain sections were immunostained for serotonin transporter (SERT). Stereological analysis revealed that epileptic rats, as compared to controls, had approximately 30% less 5-HT-stained cells in the interfascicular part of the DR, but twice as many 5-HT-stained cells in the MnR. Another finding was the reorganization of the 5-HT fiber network in all target areas analyzed, as indicated by the rightward shift of the density-size distribution histograms of SERT-stained fiber varicosities. Nonlinear regression analysis of these histograms revealed that SERT-stained varicosities were represented by two subpopulations characterized by distinct cross-sectional areas. The areal density of the small-sized varicosities was decreased in the DG (hilus and molecular layer), IL cortex (layers II/III) and MS, while that of the larger-sized varicosities was increased. The present results support the hypothesis that chronic epilepsy can trigger profound structural reorganization of the ascending serotonergic pathways in the rat brain.
癫痫动物模型研究表明，中缝核与大脑边缘系统之间的 5-羟色胺（5-HT）传递受损。本研究的目的是评估癫痫对背侧（DR）和中缝核（MnR）结构完整性的影响，以及对齿状回（DG）、下边缘皮层（IL）和内侧隔核（MS）内 5-羟色胺能纤维终末形态的影响。该研究使用海人酸（9.5mg/kg）癫痫持续状态（SE）模型在成年 Wistar 大鼠中进行。SE 后 4 个月，对动物的脑干切片进行 5-HT 免疫染色，而对前脑切片进行 5-羟色胺转运体（SERT）免疫染色。体视学分析显示，与对照组相比，癫痫大鼠在 DR 的束间部分 5-HT 染色细胞减少约 30%，但 MnR 中的 5-HT 染色细胞增加了两倍。另一个发现是所有分析的靶区 5-HT 纤维网络的重组，这表明 SERT 染色纤维末梢的密度-大小分布直方图向右移动。对这些直方图的非线性回归分析表明，SERT 染色的末梢由两个具有不同横截面积的亚群组成。DG（门区和分子层）、IL 皮质（II/III 层）和 MS 中小末梢的面积密度降低，而较大末梢的面积密度增加。这些结果支持慢性癫痫可能引发大鼠大脑中升序 5-羟色胺能通路发生深刻结构重组的假设。
