Aksic Milan, Poleksic Joko, Aleksic Dubravka, Petronijevic Natasa, Radonjic Nevena V, Jakovcevski Maja, Kapor Slobodan, Divac Nevena, Filipovic Branislav R, Jakovcevski Igor
Institute of Anatomy Niko Miljanić, School of Medicine, University of Belgrade, Belgrade, Serbia.
Institute of Medical and Clinical Biochemistry, School of Medicine, University of Belgrade, Belgrade, Serbia.
Front Neuroanat. 2021 Jun 8;15:670766. doi: 10.3389/fnana.2021.670766. eCollection 2021.
Early life stress has profound effects on the development of the central nervous system. We exposed 9-day-old rat pups to a 24 h maternal deprivation (MD) and sacrificed them as young adults (60-day-old), with the aim to study the effects of early stress on forebrain circuitry. We estimated numbers of various immunohistochemically defined interneuron subpopulations in several neocortical regions and in the hippocampus. MD rats showed reduced numbers of parvalbumin-expressing interneurons in the CA1 region of the hippocampus and in the prefrontal cortex, compared with controls. Numbers of reelin-expressing and calretinin-expressing interneurons were also reduced in the CA1 and CA3 hippocampal areas, but unaltered in the neocortex of MD rats. The number of calbinin-expressing interneurons in the neocortex was similar in the MD rats compared with controls. We analyzed cell death in 15-day-old rats after MD and found no difference compared to control rats. Thus, our results more likely reflect the downregulation of markers than the actual loss of interneurons. To investigate synaptic activity in the hippocampus we immunostained for glutamatergic and inhibitory vesicular transporters. The number of inhibitory synapses was decreased in the CA1 and CA3 regions of the hippocampus in MD rats, with the normal number of excitatory synapses. Our results indicate complex, cell type-specific, and region-specific alterations in the inhibitory circuitry induced by maternal deprivation. Such alterations may underlie symptoms of MD at the behavioral level and possibly contribute to mechanisms by which early life stress causes neuropsychiatric disorders, such as schizophrenia.
早期生活应激对中枢神经系统的发育具有深远影响。我们将9日龄的幼鼠暴露于24小时的母婴分离（MD）环境中，并在它们成年（60日龄）时将其处死，目的是研究早期应激对前脑回路的影响。我们估计了几个新皮层区域和海马体中各种通过免疫组织化学定义的中间神经元亚群的数量。与对照组相比，MD大鼠海马体CA1区和前额叶皮层中表达小白蛋白的中间神经元数量减少。海马体CA1区和CA3区中表达Reelin和钙视网膜蛋白的中间神经元数量也减少，但MD大鼠新皮层中的数量未改变。与对照组相比，MD大鼠新皮层中表达钙结合蛋白的中间神经元数量相似。我们分析了MD后15日龄大鼠的细胞死亡情况，发现与对照大鼠没有差异。因此，我们的结果更可能反映标记物的下调而非中间神经元的实际损失。为了研究海马体中的突触活动，我们对谷氨酸能和抑制性囊泡转运体进行了免疫染色。MD大鼠海马体CA1区和CA3区的抑制性突触数量减少，兴奋性突触数量正常。我们的结果表明，母婴分离诱导的抑制性回路存在复杂的、细胞类型特异性和区域特异性改变。这些改变可能是MD行为水平症状的基础，并可能有助于解释早期生活应激导致精神疾病（如精神分裂症）的机制。
