Abstract

Intermittent theta-burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation, is considered a potential therapy for treatment-resistant depression. The synaptic mechanism of iTBS has long been known to be an effective method to induce long-term potentiation (LTP)-like plasticity in humans. However, there is limited evidence as to whether the antidepressant effect of iTBS is associated with change in synaptic function in the prefrontal cortex (PFC) in preclinical study. Hence, we applied an antidepressant (i.e., fluoxetine)-resistant depression rat model induced by severe foot-shocks to investigate the antidepressant efficacy of iTBS in the synaptic pathology. The results showed that iTBS treatment improved not only the impaired LTP, but also the aberrant long-term depression in the PFC of antidepressant-resistant depression model rats. Moreover, the mechanism of LTP improvement by iTBS involved downstream molecules of brain-derived neurotrophic factor, while the mechanism of long-term depression improvement by iTBS involved downstream molecules of proBDNF. The aberrant spine morphology was also improved by iTBS treatment. This study demonstrated that the mechanism of the iTBS paradigm is complex and may regulate not only excitatory but also inhibitory synaptic effects in the PFC.

中文翻译：

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抗抑郁药耐药抑郁症大鼠模型中前额皮质突触病理学的间歇性 Theta 突发刺激机制。

 抽象的

间歇性θ脉冲刺激（iTBS）是一种重复经颅磁刺激，被认为是治疗难治性抑郁症的潜在疗法。 iTBS 的突触机制长期以来被认为是诱导人类长时程增强 (LTP) 样可塑性的有效方法。然而，在临床前研究中，关于 iTBS 的抗抑郁作用是否与前额皮质 (PFC) 突触功能变化相关的证据有限。因此，我们应用严重足部电击诱导的抗抑郁药（即氟西汀）耐药性抑郁大鼠模型来研究 iTBS 在突触病理学中的抗抑郁功效。结果表明，iTBS 治疗不仅改善了抗抑郁药耐药抑郁模型大鼠受损的 LTP，还改善了 PFC 中异常的长期抑郁。此外，iTBS改善LTP的机制涉及脑源性神经营养因子下游分子，而iTBS改善长期抑郁的机制涉及proBDNF下游分子。 iTBS 治疗也改善了异常的脊柱形态。这项研究表明，iTBS 范式的机制很复杂，不仅可以调节 PFC 中的兴奋性突触效应，还可以调节抑制性突触效应。