TY - JOUR
T1 - Antidepressant-like effects of transcorneal electrical stimulation in rat models
AU - Yu, Wing Shan
AU - Tse, Anna Chung Kwan
AU - Guan, Li
AU - Chiu, Jennifer Lok Yu
AU - Tan, Shawn Zheng Kai
AU - Khairuddin, Sharafuddin
AU - Agadagba, Stephen Kugbere
AU - Lo, Amy Cheuk Yin
AU - Fung, Man Lung
AU - Chan, Ying Shing
AU - Chan, Leanne Lai Hang
AU - Lim, Lee Wei
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/5/1
Y1 - 2022/5/1
N2 - 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.
AB - 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.
KW - Anxiety
KW - Chronic unpredictable stress
KW - Depression
KW - Retinal degeneration
KW - Transcorneal electrical stimulation
UR - http://www.scopus.com/inward/record.url?scp=85131385861&partnerID=8YFLogxK
U2 - 10.1016/j.brs.2022.05.018
DO - 10.1016/j.brs.2022.05.018
M3 - Article
C2 - 35640844
AN - SCOPUS:85131385861
SN - 1935-861X
VL - 15
SP - 843
EP - 856
JO - Brain Stimulation
JF - Brain Stimulation
IS - 3
ER -