Chen Fenghua, Polsinelli Benedetta, Nava Nicoletta, Treccani Giulia, Elfving Betina, Müller Heidi K, Musazzi Laura, Popoli Maurizio, Nyengaard Jens R, Wegener Gregers
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark; Core Center for Molecular Morphology, Section for Stereology and Microscopy, Department of Clinical Medicine, Aarhus University, Denmark.
Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari and Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Milan, Italy.
Neuroscience. 2020 Jul 1;438:100-115. doi: 10.1016/j.neuroscience.2020.05.001. Epub 2020 May 12.
Stress plays a crucial role in the pathogenesis of psychiatric disorders and affects neuronal plasticity in different brain regions. We have previously found that acute foot-shock (FS) stress elicits fast and long-lasting functional and morphological remodeling of excitatory neurons in the prefrontal cortex (PFC), which were partly prevented by the pretreatment with antidepressants. Here we investigated, whether acute stress and pretreatment with desipramine (DMI) interfere in hippocampal dendritic remodeling. Male Sprague-Dawley rats were subjected to acute FS-stress, followed by measurement of time-dependent (1, 7 and 14 days) structural plasticity (dendritic arborization, spine number and morphology) in hippocampal CA1 pyramidal neurons and expression patterns of molecular markers implicated in neuronal plasticity. We found that acute stress significantly decreased spine number, dendritic length, and altered spine morphometric parameters at all time points evaluated after stress. This was paralleled by changes in the gene expression of Spinophilin and Cdc42, and protein expression of homer1. Pretreatment with DMI prevented the stress-induced dendritic atrophy and spine loss 14 days after acute FS. However, DMI treatment without stress differentially affected the expression patterns of spine-related genes and proteins. In conclusion, acute FS-stress and pretreatment with DMI significantly changed dendritic morphology, including number and morphology of spines, and the length of dendrites in hippocampal CA1 pyramidal cells as early as 1 day, and sustained up to 14 days after acute FS. The findings were paralleled by changes in gene and protein expression of actin binding and cytoskeletal proteins, Rho GTPases, and postsynaptic scaffolding proteins.
应激在精神疾病的发病机制中起关键作用，并影响不同脑区的神经元可塑性。我们之前发现，急性足部电击（FS）应激可引发前额叶皮质（PFC）中兴奋性神经元快速且持久的功能和形态重塑，而抗抑郁药预处理可部分预防这种重塑。在此，我们研究了急性应激和地昔帕明（DMI）预处理是否会干扰海马树突重塑。对雄性Sprague-Dawley大鼠施加急性FS应激，随后测量海马CA1锥体神经元中随时间变化（1、7和14天）的结构可塑性（树突分支、棘突数量和形态）以及与神经元可塑性相关的分子标记的表达模式。我们发现，急性应激在应激后评估的所有时间点均显著减少了棘突数量、树突长度，并改变了棘突形态学参数。这与亲嗜素和Cdc42的基因表达以及homer1的蛋白表达变化相平行。急性FS应激14天后，DMI预处理可预防应激诱导的树突萎缩和棘突丢失。然而，无应激的DMI处理对棘突相关基因和蛋白的表达模式有不同影响。总之，急性FS应激和DMI预处理早在急性FS应激1天后就显著改变了海马CA1锥体细胞的树突形态，包括棘突的数量和形态以及树突长度，并持续至急性FS应激后14天。这些发现与肌动蛋白结合蛋白和细胞骨架蛋白、Rho GTP酶以及突触后支架蛋白的基因和蛋白表达变化相平行。
