Low field magnetic stimulation promotes myelin repair and cognitive recovery in chronic cuprizone mouse model

Abstract

Background Multiple sclerosis (MS) is an inflammatory demyelinating disease featured with neuroinflammation, demyelination, and the loss of oligodendrocytes. Cognitive impairment and depression are common neuropsychiatric symptoms in MS that are poorly managed with the present interventions. Objective This study aimed to investigate the effects of low field magnetic stimulation (LFMS), a novel non‐invasive neuromodulation technology, on cognitive impairment and depressive symptoms associated with MS using a mouse model of demyelination. Methods C57BL female mice were fed with a 0.2% cuprizone diet for 12 weeks to induce a chronic demyelinating model followed by 4 weeks of cuprizone withdrawal with either sham or LFMS treatment. Results Improved cognition and depression‐like behaviour and restored weight gain were observed in mice with LFMS treatment. Immunohistochemical and immunoblotting data showed enhanced myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein expressions (MOG) in the prefrontal cortex of mice with LFMS treatment, supporting that myelin repair was promoted. LFMS also increased the protein expression of mature oligodendrocyte biomarker glutathione‐S‐transferase (GST‐π). In addition, expression of TGF‐β and associated receptors were elevated with LFMS treatment, implicating this pathway in the response. Conclusion Results from the present study revealed LFMS to have neuroprotective effects, suggesting that LFMS has potential therapeutic value for treating cognitive impairment and depression related to demyelination disorders.

Low‑field magnetic stimulation improved cuprizone‑induced depression‑like symptoms and demyelination in female mice

“…Both MS and major depressive disorder share the common pathophysiology of demyelination of CNS regions and are associated with neuro-inflammation processes (55,56). Indeed, previous CPZ mouse models have reported depression-like symptoms and myelin deficiency (19,30) demonstrating a possible correlation between depression and demyelination of the CNS. In the present study, it was demonstrated that mice fed with CPZ exhibited markedly reduced MBP staining density within the PFC and HPC after only 3 weeks, which suggested that there was a possible link between early depression and myelin damage in this demyelinating disease model.…”

“…The LFMS device is composed of two 360 mm-diameter coils and a control center that generates intermittent gamma stimulation waves (Beijing Antis Biotech Co., Ltd.). The LFMS parameter settings were based on our previous in vivo and in vitro studies (28)(29)(30)37). Briefly, the magnetic field alternated every 2 min between approximate and linear gradients.…”

“…Mice exhibiting normal behavior remember the arm they have already explored and will enter one of the other arms of the maze ( 19 ). The Y maze apparatus was built in house and previously described ( 19 , 30 ). Briefly, each mouse was placed at the end of arm A and allowed to freely explore all three arms for 5 min.…”

“…Y-maze spontaneous alternation test. The Y-Maze is widely used to evaluate spatial working memory (39) and has been previously used to detect memory deficits in CPZ models in numerous studies (18,30,40,41). Mice exhibiting normal behavior remember the arm they have already explored and will enter one of the other arms of the maze (19).…”

“…In our previous study, we demonstrated that 40 Hz LFMS restored cognitive and motor functions in an animal model of traumatic brain injury ( 28 ) and enhanced the differentiation of oligodendrocyte progenitor cells in vitro ( 29 ). More recently, LFMS stimulation has been reported to promote myelin repair in the prefrontal cortex (PFC) and improves cognition and depression-like symptoms in a chronic CPZ mouse model ( 30 ). Together, these findings support the hypothesis that LFMS will improve depressive symptoms and CI, while restoring demyelination in an acute CPZ-induced mouse model of MS.…”