Transcorneal electrical stimulation: Potential treatment for depression and dementia

Transcorneal electrical stimulation (TES), a noninvasive treatment modality involving stimulation of corneal surface of the eyes, provides antidepressant-like effects and improves cognitive function in animal models, according to researchers from the University of Hong Kong (HKU) and City University of Hong Kong (CityU).

Deep brain stimulation of the prefrontal cortex was reported to improve memory function and relieve depressive symptoms in an animal study in 2015. These therapeutic effects were attributed to the growth of neurons in the hippocampus, a region of the brain known to be involved in learning and memory function. [Transl Psychiatry 2015;5:e535] “However, this technique is invasive and requires surgery to implant electrodes in the brain, which may cause side effects such as infections and other postoperative complications. We have been looking for alternative ways to treat neuropsychiatric diseases,” said the researchers.

“TES is a noninvasive modality initially developed to treat eye diseases. It would be a major scientific breakthrough if it could be applied to treat neuropsychiatric disease,” said Dr Leanne Chan of the Department of Electrical Engineering, CityU.

In view of this, the researchers examined the antidepressant effect of TES in two groups of rat models of depression – an S334ter-line-3 rat model and a chronic unpredictable stress (CUS) rat model. [Brain Stimul 2022;15:843-856]

TES, administered daily for 1 week, activated brain pathways, resulting in anxiolytic and antidepressant-like effects in S334ter-line-3 rats. “[In the CUS rat model], this technique reduced stress hormone [ie, corticosterone] and induced the expression of genes involved in development and growth of brain cells in the hippocampus,” said the researchers. “The overall findings suggest a possible neuroplasticity mechanism of the antidepressant-like effects of TES.”

In a related experiment, the researchers investigated whether TES could be used to treat dementia in two mouse models of impaired memory function, including aged mice and a FXFAD model of Alzheimer’s disease.

Results showed that TES treatment (5 days/week for 3 weeks) substantially improved memory performance in both aged and 5XFAD mice in memory tests. In addition, TES also ameliorated beta-amyloid plaque deposition in male, but not female, 5XFAD mice, indicating that reduced amyloid plaques and the associated neurotoxic pathologies could be the underlying mechanism for the memory improvement induced by TES. [Ann N Y Acad Sci 2022;doi: 10.1111/nyas.14850]

“Overall, these findings support further investigation of TES as a potential treatment for cognitive dysfunction and mechanistic studies of effects of TES in other dementia models,” said the researchers.

“Although it would be rational to speculate that the TES-induced memory improvement in male 5XFAD mice is due to reduction of amyloid plaques, the failure to clear amyloid plaques in female 5XFAD mice suggests the involvement of other mechanisms,” the researchers commented. “Notably, TES significantly reversed the down-regulated level of postsynaptic protein 95 in the hippocampus of male 5XFAD mice, suggesting the effects of TES involve a postsynaptic mechanism.”

“These research findings pave the way for new therapeutic opportunities to develop novel treatment for patients suffering from treatment-resistant depression and dementia,” summarized Dr Ying-Sing Chan of the Neuroscience Research Centre, HKU.