Differential microstructural alterations in rat cerebral cortex in a model of chronic mild stress depression.
Differential microstructural alterations in rat cerebral cortex in a model of chronic mild stress depression.
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DOI：
10.1371/journal.pone.0192329
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Jespersen SN
中科院分区：
文献类型：
--
作者：
Khan AR;Kroenke CD;Wiborg O;Chuhutin A;Nyengaard JR;Hansen B;Jespersen SN
慢性轻度压力在许多情况下会导致抑郁症，并与包括精神障碍在内的几种使人衰弱的疾病有关。最近，神经元示踪技术，体视学，免疫组织化学显示海马，下丘脑，前额叶皮层和杏仁核，形成了一个相互关联的系统称为压力电路的持续和显着的微观结构的变化。大多数研究只关注这个回路，然而，一些研究表明，感觉和运动系统的操纵可能会影响情绪障碍的发生和治疗，因此在研究应激和抑郁时大脑微结构的改变时，这些区域不应被忽视。为此，我们探讨了在慢性轻度应激抑郁症模型中不同皮质区域的微结构改变。该研究采用离体扩散MRI（d-MRI）评估应激（快感缺失和弹性）和对照动物的皮质微结构。MRI随后进行免疫组化以证实d-MRI结果。我们发现，在听觉皮层（AC）的应力组和弹性组的各向异性分数显着较高的细胞外扩散率显着降低。与对照组相比，在应力组的任何皮质ROI中均未发现神经突密度显著更高，尽管应力组的轴突密度更高。我们还报告显着变薄的运动皮层（MC）在这两个压力组。这与最近对抑郁症和类似疾病的临床和临床前研究一致，其中在AC和MC中发现了显著的微观结构和代谢改变。我们的研究结果提供了进一步的证据表明，AC和MC是敏感的压力暴露，并可能扩大我们的理解的微观结构的影响，压力以外的压力电路的大脑。这一领域的进展可能为抑郁症及相关疾病的诊断和治疗干预提供新的研究途径。
Chronic mild stress leads to depression in many cases and is linked to several debilitating diseases including mental disorders. Recently, neuronal tracing techniques, stereology, and immunohistochemistry have revealed persistent and significant microstructural alterations in the hippocampus, hypothalamus, prefrontal cortex, and amygdala, which form an interconnected system known as the stress circuit. Most studies have focused only on this circuit, however, some studies indicate that manipulation of sensory and motor systems may impact genesis and therapy of mood disorders and therefore these areas should not be neglected in the study of brain microstructure alterations in response to stress and depression. For this reason, we explore the microstructural alterations in different cortical regions in a chronic mild stress model of depression. The study employs ex-vivo diffusion MRI (d-MRI) to assess cortical microstructure in stressed (anhedonic and resilient) and control animals. MRI is followed by immunohistochemistry to substantiate the d-MRI findings. We find significantly lower extracellular diffusivity in auditory cortex (AC) of stress groups and a significantly higher fractional anisotropy in the resilient group. Neurite density was not found to be significantly higher in any cortical ROIs in the stress group compared to control, although axonal density is higher in the stress groups. We also report significant thinning of motor cortex (MC) in both stress groups. This is in agreement with recent clinical and preclinical studies on depression and similar disorders where significant microstructural and metabolic alterations were found in AC and MC. Our findings provide further evidence that the AC and MC are sensitive towards stress exposure and may extend our understanding of the microstructural effects of stress beyond the stress circuit of the brain. Progress in this field may provide new avenues of research to help in diagnosis and treatment intervention for depression and related disorders.
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影响因子：
3.7
作者：
Delgado y Palacios R;Verhoye M;Henningsen K;Wiborg O;Van der Linden A
通讯作者：
Van der Linden A
影响因子：
3.3
作者：
Assaf, Y;Freidlin, RZ;Basser, PJ
通讯作者：
Basser, PJ
影响因子：
3
作者：
Cardinale, Francesco;Chinnici, Giuseppa;Ferrigno, Giancarlo
通讯作者：
Ferrigno, Giancarlo
影响因子：
2.3
作者：
Bose, Mitali;Munoz-Llancao, Pablo;Roychowdhury, Swagata;Nichols, Justin A.;Jakkamsetti, Vikram;Porter, Benjamin;Byrapureddy, Rajasekhar;Salgado, Humberto;Kilgard, Michael P.;Aboitiz, Francisco;Dagnino-Subiabre, Alexies;Atzori, Marco
通讯作者：
Atzori, Marco
影响因子：
3.1
作者：
Drevets, Wayne C.;Price, Joseph L.;Furey, Maura L.
通讯作者：
Furey, Maura L.