Antidepressant-like effects of transcorneal electrical stimulation in rat models

• Published in: Brain stimulation 2022-05, Vol.15 (3), p.843-856
• Main Authors: Yu, Wing Shan, Tse, Anna Chung-Kwan, Guan, Li, Chiu, Jennifer Lok Yu, Tan, Shawn Zheng Kai, Khairuddin, Sharafuddin, Agadagba, Stephen Kugbere, Lo, Amy Cheuk Yin, Fung, Man-Lung, Chan, Ying-Shing, Chan, Leanne Lai Hang, Lim, Lee Wei
• Format: Article
• Language: English
• Subjects: Anxiety; Chronic unpredictable stress; Depression; Retinal degeneration; Transcorneal electrical stimulation
• ISSN: 1935-861X; 1876-4754
• DOI: 10.1016/j.brs.2022.05.018

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. •TES induced antidepressant-like activities in S334ter-line-3 rat model of retinal degeneration.•TES induced antidepressant-like effects through both neurogenesis-dependent and -independent mechanisms in CUS-induced rat model of depression.•TES reduced plasma corticosterone levels and upregulated neurogenesis-related gene expression.•TES normalized protein expression of apoptotic and neuroplasticity markers in the hippocampus and amygdala.