Antidepressant-like effects of transcorneal electrical stimulation in rat models

Wing Shan Yu, Anna Chung Kwan Tse, Li Guan, Jennifer Lok Yu Chiu, Shawn Zheng Kai Tan, Sharafuddin Khairuddin, Stephen Kugbere Agadagba, Amy Cheuk Yin Lo, Man Lung Fung, Ying Shing Chan, Leanne Lai Hang Chan*, Lee Wei Lim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Background: 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. Objective: 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). Methods: 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. Results: 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. Conclusion: The overall findings suggest a possible neuroplasticity mechanism of the antidepressant-like effects of TES.

Original languageEnglish
Pages (from-to)843-856
Number of pages14
JournalBrain Stimulation
Volume15
Issue number3
DOIs
Publication statusPublished - 1 May 2022
Externally publishedYes

Keywords

  • Anxiety
  • Chronic unpredictable stress
  • Depression
  • Retinal degeneration
  • Transcorneal electrical stimulation

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