School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Department of Electrical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
Brain Stimul. 2022 May-Jun;15(3):843-856. doi: 10.1016/j.brs.2022.05.018. Epub 2022 May 28.
Given that visual impairment is bi-directionally associated with depression, we examined whether transcorneal electrical stimulation (TES), a non-invasive treatment for visual disorders, can ameliorate depressive symptoms.
The putative antidepressant-like effects of TES and the underlying mechanisms were investigated in an S334ter-line-3 rat model of retinal degeneration and a rat model of chronic unpredictable stress (CUS).
TES was administered daily for 1 week in S334ter-line-3 and CUS rats. The effects of TES on behavioral parameters, plasma corticosterone levels, and different aspects of neuroplasticity, including neurogenesis, synaptic plasticity, and apoptosis, were examined.
In S334ter-line-3 rats, TES induced anxiolytic and antidepressant-like behaviors in the cylinder, open field, home cage emergence, and forced swim tests. In the CUS rat model, TES induced hedonic-like behavior and decreased behavioral despair, which were accompanied by reduced plasma corticosterone levels and upregulated expression of neurogenesis-related genes. Treatment with the neurogenesis blocker temozolomide only inhibited the hedonic-like effect of TES, suggesting the antidepressant-like effects of TES were mediated through both neurogenesis-dependent and -independent mechanisms. Furthermore, TES was found to normalize the protein expression of synaptic markers and apoptotic Bcl-2-associated X protein in the hippocampus and amygdala in the CUS rat model. The improvements in neuroplasticity may involve protein kinase B (AKT) and protein kinase A (PKA) signaling pathways in the hippocampus and amygdala, respectively, as demonstrated by the altered pAKT/AKT and pPKA/PKA ratios.
The overall findings suggest a possible neuroplasticity mechanism of the antidepressant-like effects of TES.
鉴于视力障碍与抑郁呈双向关联，我们研究了经角膜电刺激（TES）作为一种治疗视觉障碍的非侵入性方法是否可以改善抑郁症状。
在 S334ter-line-3 视网膜变性大鼠模型和慢性不可预测性应激（CUS）大鼠模型中，研究 TES 的潜在抗抑郁样作用及其潜在机制。
在 S334ter-line-3 大鼠和 CUS 大鼠中，每天进行 TES 治疗 1 周。检测 TES 对行为参数、血浆皮质酮水平以及神经可塑性的不同方面（包括神经发生、突触可塑性和细胞凋亡）的影响。
在 S334ter-line-3 大鼠中，TES 诱导了圆柱、旷场、笼内出现和强迫游泳测试中的抗焦虑和抗抑郁样行为。在 CUS 大鼠模型中，TES 诱导了快感样行为，降低了行为绝望，同时降低了血浆皮质酮水平并上调了神经发生相关基因的表达。神经发生抑制剂替莫唑胺的处理仅抑制了 TES 的快感样作用，表明 TES 的抗抑郁样作用是通过神经发生依赖和非依赖机制介导的。此外，发现 TES 可使 CUS 大鼠模型海马和杏仁核中突触标志物和凋亡 Bcl-2 相关 X 蛋白的蛋白表达正常化。神经可塑性的改善可能涉及海马和杏仁核中蛋白激酶 B（AKT）和蛋白激酶 A（PKA）信号通路，分别表现为 pAKT/AKT 和 pPKA/PKA 比值的改变。
总体研究结果表明 TES 的抗抑郁样作用可能涉及神经可塑性机制。
