Csabai Dávid, Wiborg Ove, Czéh Boldizsár
MTA - PTE, Neurobiology of Stress Research Group, Szentágothai Research Centre, University of Pécs, Pécs, Hungary.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Front Cell Neurosci. 2018 Jan 30;12:24. doi: 10.3389/fncel.2018.00024. eCollection 2018.
Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I) and symmetric (Type II) synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 10 asymmetric synapses, 1.06 × 10 symmetric synapses and 1.00 × 10 myelinated axons. The density of asymmetric synapses was 5.5/μm and the density of symmetric synapses was 0.5/μm. Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network connectivity is likely to form the anatomical basis for the impaired functioning of this brain area. Indeed, impaired functioning of the prefrontal cortex, such as cognitive deficits are common in stressed individuals as well as in depressed patients.
应激经历可诱导边缘系统神经元发生结构变化。这些细胞变化有助于应激诱导的精神病理学如抑郁症的发展。在长期应激动物的前额叶皮质中，已有报道树突长度缩短和树突棘丢失。由于树突表面减少，这种树突物质的丢失也应导致突触丢失。但到目前为止，还没有人研究长期应激动物前额叶皮质中的突触数量。在此，我们研究了采用抑郁症动物模型的大鼠的突触联系，该模型中动物暴露于慢性应激方案。我们的假设是长期应激应减少内侧前额叶皮质中轴突 - 棘突触的数量。成年雄性大鼠每天接受应激处理9周，之后我们进行了死后定量电子显微镜分析，以量化边缘下皮质中突触的数量和形态。我们分析了对照大鼠和应激大鼠所有皮质层中的不对称（I型）和对称（II型）突触。我们还量化了轴突数量并测量了边缘下皮质的体积。在我们的系统无偏分析中，总共检查了21,000个轴突终末。我们在对照大鼠的边缘下皮质中发现了以下数量：1.15×10个不对称突触、1.06×10个对称突触和1.00×10个有髓轴突。不对称突触的密度为5.5/μm，对称突触的密度为0.5/μm。平均突触膜长度为207nm，平均轴突终末膜长度为489nm。应激减少了较深皮质层中的突触和有髓轴突数量，而突触膜长度增加。这些应激诱导的超微结构变化表明边缘下皮质的神经元皮质网络连接性降低。这种降低的网络连接性可能构成该脑区功能受损的解剖学基础。事实上，前额叶皮质功能受损，如认知缺陷，在应激个体以及抑郁症患者中都很常见。
