Abstract:
Depression is a mood disorder coursing with several behavioral, cellular, and neurochemical alterations. The negative impact of chronic stress may precipitate this neuropsychiatric disorder. Interestingly, downregulation of oligodendrocyte-related genes, abnormal myelin structure, and reduced numbers and density of oligodendrocytes in the limbic system have been identified in patients diagnosed with depression, but also in rodents exposed to chronic mild stress (CMS). Several reports have emphasized the importance of pharmacological or stimulation-related strategies in influencing oligodendrocytes in the hippocampal neurogenic niche. Repetitive transcranial magnetic stimulation (rTMS) has gained attention as an intervention to revert depression. Here, we hypothesized that 5 Hz (Hz) of rTMS or Fluoxetine (Flx) would revert depressive-like behaviors by influencing oligodendrocytes and revert neurogenic alterations caused by CMS in female Swiss Webster mice. Our results showed that 5 Hz rTMS or Flx revert depressive-like behavior. Only rTMS influenced oligodendrocytes by increasing the number of Olig2-positive cells in the hilus of the dentate gyrus and the prefrontal cortex. However, both strategies exerted effects on some events of the hippocampal neurogenic processes, such as cell proliferation (Ki67-positive cells), survival (CldU-positive cells), and intermediate stages (doublecortin-positive cells) along the dorsal-ventral axis of this region. Interestingly, the combination of rTMS-Flx exerted antidepressant-like effects, but the increased number of Olig2-positive cells observed in mice treated only with rTMS was canceled. However, rTMS-Flx exerted a synergistic effect by increasing the number of Ki67-positive cells. It also increased the number of CldU- and doublecortin-positive cells in the dentate gyrus. Our results demonstrate that 5 Hz rTMS has beneficial effects, as it reverted depressive-like behavior by increasing the number of Olig2-positive cells and reverting the decrement in hippocampal neurogenesis in CMS-exposed mice. Nevertheless, the effects of rTMS on other glial cells require further investigation.
摘要:
抑郁症是一种情绪障碍,伴随着几种行为,细胞,和神经化学变化。慢性压力的负面影响可能会加剧这种神经精神障碍。有趣的是,少突胶质细胞相关基因的下调,髓鞘结构异常,在诊断为抑郁症的患者中,已经发现边缘系统中少突胶质细胞的数量和密度减少,而且在暴露于慢性轻度应激(CMS)的啮齿动物中也是如此。一些报道强调了药理学或刺激相关策略在影响海马神经源性生态位中的少突胶质细胞中的重要性。重复经颅磁刺激(rTMS)作为恢复抑郁症的干预措施已引起关注。这里,我们假设5Hz(Hz)的rTMS或氟西汀(Flx)将通过影响少突胶质细胞来恢复抑郁样行为,并恢复雌性SwissWebster小鼠CMS引起的神经源性改变.我们的结果表明,5HzrTMS或Flx可以恢复类似抑郁的行为。只有rTMS通过增加齿状回和前额叶皮层中Olig2阳性细胞的数量来影响少突胶质细胞。然而,两种策略都对海马神经发生过程的一些事件产生影响,如细胞增殖(Ki67阳性细胞),存活(CldU阳性细胞),以及沿该区域背-腹轴的中间阶段(dublecoortin阳性细胞)。有趣的是,rTMS-Flx的组合发挥了抗抑郁样作用,但在仅用rTMS治疗的小鼠中观察到的Olig2阳性细胞数量的增加被取消。然而,rTMS-Flx通过增加Ki67阳性细胞的数量发挥协同作用。它还增加了齿状回中CldU和dublecoortin阳性细胞的数量。我们的结果表明,5HzrTMS具有有益的效果,因为它通过增加CMS暴露小鼠中Olig2阳性细胞的数量和海马神经发生的减少来恢复抑郁样行为。然而,rTMS对其他胶质细胞的影响需要进一步研究.