背景:结构MRI已证实抑郁症病理和抗抑郁药治疗的脑部改变。虽然突触可塑性先前已被提出作为细胞和分子尺度的MRI发现的潜在潜在机制,仍然没有足够的证据将抑郁症病理学中的MRI发现与突触可塑性机制联系起来。
方法:在本研究中,Wistar-Kyoto(WKY)抑郁症大鼠模型用抗抑郁药(西酞普兰或Jie-Yu丸)治疗,并在一系列行为测试和7.0MRI扫描仪中进行测试。然后,我们测量了改变的大脑区域内的树突状脊柱密度。我们还检查了突触标记蛋白(PSD-95和SYP)的表达。
结果:WKY大鼠在蔗糖偏好试验(SPT)和强迫游泳试验(FST)中表现出抑郁样行为,以及空场测试(OFT)中的焦虑样行为。两种抗抑郁药均逆转了SPT和OFT的行为变化,但未逆转FST。我们发现SPT表现与MRI检测到的脑体积之间存在相关性。所有结构变化均与call体(白质)的改变一致,树突棘密度,以及PSD95和SYP在不同水平的表达。两种抗抑郁药类似地逆转了这些宏观和微观变化。
结论:单剂量抗抑郁药是本研究的主要局限性。进一步的研究应集中在白质微结构的改变和髓鞘相关蛋白的改变。除了比较氯胺酮的效果。
结论:转化证据将MRI结构改变和突触可塑性改变联系在一起,这促进了我们对WKY大鼠SPT机制和抗抑郁反应的理解。
BACKGROUND: Structural MRI has demonstrated brain alterations in depression pathology and antidepressants treatment. While synaptic plasticity has been previously proposed as the potential underlying mechanism of MRI findings at a cellular and molecular scale, there is still insufficient evidence to link the MRI findings and synaptic plasticity mechanisms in depression pathology.
METHODS: In this study, a Wistar-Kyoto (WKY) depression rat model was treated with antidepressants (citalopram or Jie-Yu Pills) and tested in a series of behavioral tests and a 7.0 MRI scanner. We then measured dendritic spine density within altered brain regions. We also examined expression of synaptic marker proteins (PSD-95 and SYP).
RESULTS: WKY rats exhibited depression-like behaviors in the sucrose preference test (SPT) and forced swim test (FST), and anxiety-like behaviors in the open field test (OFT). Both antidepressants reversed behavioral changes in SPT and OFT but not in FST. We found a correlation between SPT performance and brain volumes as detected by MRI. All structural changes were consistent with alterations of the corpus callosum (white matter), dendritic spine density, as well as PSD95 and SYP expression at different levels. Two antidepressants similarly reversed these macro- and micro-changes.
CONCLUSIONS: The single dose of antidepressants was the major limitation of this study. Further studies should focus on the white matter microstructure changes and myelin-related protein alterations, in addition to comparing the effects of ketamine.
CONCLUSIONS: Translational evidence links structural MRI changes and synaptic plasticity alterations, which promote our understanding of SPT mechanisms and antidepressant response in WKY rats.