Burst-firing patterns in the prefrontal cortex underlying the neuronal mechanisms of depression probed by antidepressants
Burst-firing patterns in the prefrontal cortex underlying the neuronal mechanisms of depression probed by antidepressants
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抗抑郁药探究抑郁症神经元机制背后的前额皮质爆发放电模式
DOI：
10.1111/ejn.12725
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发表时间：
2014-11-01
影响因子：
3.4
通讯作者：
Li, Yang
中科院分区：
文献类型：
--
作者：
Guo, Fei;Zhang, Qi;Li, Yang
重度抑郁症（MDD）是世界范围内发病的主要原因之一。几种抗抑郁药已被广泛用于治疗MDD患者。然而，脑功能的神经元变化仍然知之甚少。基于标准的慢性轻度应激（CMS）小鼠抑郁模型，我们研究了经典抗抑郁药氟西汀和一种新的呋甾皂苷衍生物（在本研究中称为YY-23）的神经机制。结果表明，氟西汀和YY-23均使CMS诱导的抑郁样行为正常化。YY-23比氟西汀更快地引起抗抑郁样行为。在体内神经元活动方面，慢性给予氟西汀和YY-23可逆转CMS诱导的内侧前额叶皮质锥体神经元而非腹侧被盖区（VTA）爆发性自发放电减少。我们还发现，CMS诱导的前额叶脑源性神经营养因子（BDNF）表达的缺陷也恢复了长期服用YY-23和氟西汀。此外，长期给予氟西汀而不是YY-23导致对照饲养动物的抗抑郁样行为改善和VTA爆发放电变化，表明YY-23的药理学作用对CMS处理的动物具有特异性。总之，这些数据表明，锥体细胞的爆发放电模式可能是抑郁样小鼠和抗抑郁作用的神经生物标志物。此外，突触传递和BDNF可能有助于对抑郁症的快速抗抑郁样作用。
Major depressive disorder (MDD) is one of the leading causes of morbidity worldwide. Several antidepressants have been widely prescribed to treat patients with MDD. However, neuronal changes in brain function remain poorly understood. Based on the standard chronic mild stress (CMS) model of depression in mice, we investigated the neuronal mechanisms of the classic antidepressant, fluoxetine, and a new compound (termed YY-23 in this study) derived from furostanol saponin. The results showed that both fluoxetine and YY-23 normalized CMS-induced depressive-like behaviors. YY-23 caused antidepressant-like behaviors with a faster action than fluoxetine. In terms of in vivo neuronal activities, a CMS-induced decrease in spontaneous firing in burst of medial prefrontal cortex pyramidal neurons rather than ventral tegmental area (VTA) was reversed by the chronic administration of fluoxetine and YY-23. We also found that CMS-induced deficits in the expression of prefrontal brain-derived neurotrophic factor (BDNF) were also restored by chronically administering YY-23 and fluoxetine. In addition, chronic administration of fluoxetine rather than YY-23 resulted in an improvement of antidepressive-like behavior and a change of burst firing of VTA in control-housed animals, indicating that the pharmacological effects of YY-23 were specific to CMS-treated animals. Together, these data suggest that the burst-firing patterns of pyramidal cells may be a neural biomarker of depressive-like mice and antidepressant action. Furthermore, synaptic transmission and BDNF may contribute to the rapid antidepressant-like effects on depression.