Sub-chronic variable stress induces sex-specific effects on glutamatergic synapses in the nucleus accumbens.
Sub-chronic variable stress induces sex-specific effects on glutamatergic synapses in the nucleus accumbens.
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DOI：
10.1016/j.neuroscience.2017.03.014
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发表时间：
2017-05-14
期刊：
影响因子：
3.3
通讯作者：
Hodes GE
中科院分区：
文献类型：
--
作者：
Brancato A;Bregman D;Ahn HF;Pfau ML;Menard C;Cannizzaro C;Russo SJ;Hodes GE
男性和女性表现出不同的抑郁症症状，根据目前的诊断标准，女性抑郁症的发病率是女性的两倍。然而，很少有人知道这些重要的性别差异的机制。亚慢性可变压力（SCVS）是一种啮齿动物抑郁模型，仅在雌性小鼠中诱导抑郁样行为，模拟了女性对情绪障碍更敏感的临床证据。越来越多的证据表明，改变兴奋性突触的神经可塑性的核（NAc）是一个关键的病理生理特征的易感性，以社会压力的男性。在这里，我们研究了SCVS对雌性和雄性小鼠NAc中中型棘神经元突触前和突触后蛋白水平和突触形态的影响。动物经历了为期六天的暴露于交替的应激源，包括休克，尾巴悬挂和约束。来自NAc的中等多刺神经元填充有荧光黄染料，并且使用NeuronStudio检查棘密度和类型。在另一组动物中，对囊泡谷氨酸转运蛋白1（VGLUT 1）和囊泡谷氨酸转运蛋白2（VGLUT 2）进行免疫荧光染色，以标记皮质和皮质下谷氨酸能末梢。PSD 95的免疫染色用于评估突触后密度。女性表现出电路特异性突触前改变VGLUT 1和VGLUT 2包含突触，可能有助于应力易感性在PSD 95点，棘密度或类型的突触后改变的情况下。这些数据表明，在女性的压力易感性与不同的amatergic输入的NAC的频率的变化。
Men and women manifest different symptoms of depression and under current diagnostic criteria, depression is twice as prevalent in woman. However, little is known of the mechanisms contributing to these important sex differences. Sub-chronic variable stress (SCVS), a rodent model of depression, induces depression-like behaviors in female mice only, modelling clinical evidence of higher susceptibility to mood disorders in women. Accumulating evidence indicates that altered neuroplasticity of excitatory synapses in the nucleus accumbens (NAc) is a key pathophysiological feature of susceptibility to social stress in males. Here we investigated the effects of SCVS on pre- and post-synaptic protein levels and morphology of glutamatergic synapses of medium spiny neurons in the NAc of female and male mice. Animals underwent six-day exposure to alternating stressors including shock, tail suspension and restraint. Medium spiny neurons from the NAc were filled with a Lucifer yellow dye and spine density and type were examined using NeuronStudio. In a separate group of animals, immunofluorescence staining was performed for vesicular glutamate transporter 1 (VGLUT1) and vesicular glutamate transporter 2 (VGLUT2), in order to label cortical and subcortical glutamatergic terminals. Immunostaining for PSD95 was employed to evaluate post-synaptic density. Females demonstrated circuit specific pre-synaptic alterations in VGLUT1 and VGLUT2 containing synapses that may contribute to stress susceptibility in the absence of post-synaptic alterations in PSD 95 puncta, spine density or type. These data indicate that susceptibility to stress in females is associated with changes in the frequency of distinct glutamatergic inputs to the NAc.