Chen Fenghua, du Jardin Kristian Gaarn, Waller Jessica A, Sanchez Connie, Nyengaard Jens R, Wegener Gregers
Stereology and Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, DK-8000 Aarhus C, Denmark; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, DK-8240 Risskov, Denmark.
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, DK-8240 Risskov, Denmark.
Eur Neuropsychopharmacol. 2016 Feb;26(2):234-245. doi: 10.1016/j.euroneuro.2015.12.018. Epub 2015 Dec 11.
Preclinical studies reveal that the multimodal antidepressant vortioxetine enhances long-term potentiation and dendritic branching compared to a selective serotonin reuptake inhibitor (SSRI). In the present study, we investigated vortioxetine׳s effects on spines and dendritic morphology in rat hippocampus at two time points compared to the SSRI, fluoxetine. Rats were dosed for 1 and 4 weeks with vortioxetine and fluoxetine at doses relevant for antidepressant activity. Dendritic morphology of pyramidal neurons (i.e., dendritic length, dendritic branch, spine number and density, and Sholl analysis) was examined in Golgi-stained sections from hippocampal CA1. After 1 week of treatment, vortioxetine significantly increased spine number (apical and basal dendrites), spine density (only basal), dendritic length (only apical), and dendritic branch number (apical and basal), whereas fluoxetine had no effect. After 4 weeks of treatment, vortioxetine significantly increased all measures of dendritic spine morphology as did fluoxetine except for spine density of basal dendrites. The number of intersections in the apical and basal dendrites was also significantly increased for both treatments after 4 weeks compared to control. In addition, 4 weeks of vortioxetine treatment, but not fluoxetine, promoted a decrease in spine neck length. In conclusion, 1-week vortioxetine treatment induced changes in spine number and density and dendritic morphology, whereas an equivalent dose of fluoxetine had no effects. Decreased spine neck length following 4-week vortioxetine treatment suggests a transition to mature spine morphology. This implies that vortioxetine׳s effects on spine and dendritic morphology are mediated by mechanisms that go beyond serotonin reuptake inhibition.
临床前研究表明，与选择性5-羟色胺再摄取抑制剂（SSRI）相比，多模式抗抑郁药伏硫西汀可增强长时程增强效应和树突分支。在本研究中，我们比较了伏硫西汀与SSRI氟西汀在两个时间点对大鼠海马体棘突和树突形态的影响。给大鼠服用具有抗抑郁活性剂量的伏硫西汀和氟西汀1周和4周。在海马CA1区的高尔基染色切片中检查锥体神经元的树突形态（即树突长度、树突分支、棘突数量和密度以及Sholl分析）。治疗1周后，伏硫西汀显著增加了棘突数量（顶树突和基底树突）、棘突密度（仅基底树突）、树突长度（仅顶树突）和树突分支数量（顶树突和基底树突），而氟西汀没有效果。治疗4周后，伏硫西汀显著增加了所有树突棘形态指标，氟西汀也有相同效果，但基底树突的棘突密度除外。与对照组相比，4周治疗后，两种药物治疗的顶树突和基底树突中的交叉点数量也显著增加。此外，4周的伏硫西汀治疗可促进棘突颈部长度缩短，但氟西汀无此作用。总之，1周的伏硫西汀治疗可引起棘突数量、密度和树突形态的变化，而同等剂量的氟西汀则无此作用。4周伏硫西汀治疗后棘突颈部长度缩短表明向成熟棘突形态转变。这意味着伏硫西汀对棘突和树突形态的影响是由5-羟色胺再摄取抑制以外的机制介导的。
