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

Abstract

Depression is a common and disabling comorbidity of multiple sclerosis (MS), with currently no clear guidelines for treatment. Low-field magnetic stimulation (LFMS), a novel non-invasive neuromodulation intervention, has been previously demonstrated to rapidly alleviate mood disorders. The aim of the present study was to investigate the effects of LFMS on depression-like behaviors and demyelination in a well-established mouse model of MS. C57BL/6 female mice were fed a 0.2% cuprizone (CPZ) diet for 3 or 6 weeks to induce acute demyelination. During this time, the mice were treated with either sham or LFMS for 20 min/day, 5 days/week. After 3 or 6 weeks of treatment, behavior was assessed with the open field task, Y-maze and the forced swim test. The prefrontal cortex and hippocampus were then collected to perform immunohistochemistry and western blot analysis to verify myelination status. The CPZ diet did not cause significant locomotor deficits; however, working memory, measured using the Y maze, depression-like behavior and adaptive learning, assayed using the forced swim test, were significantly impaired in these animals. LFMS treatment demonstrated a significant antidepressant-like effect and markedly attenuated the CPZ-induced demyelination in the prefrontal cortex after 3-and 6-weeks of treatment, as observed by changes in myelin basic protein immunostaining and western blot analysis. Therefore, the results of the present study indicated that LFMS may be a promising therapy for demyelinating diseases due to the improvement of depressive symptoms via regulation of myelination in cortical areas.

Pinostrobin alleviates chronic restraint stress‑induced cognitive impairment by modulating oxidative stress and the function of astrocytes in the hippocampus of rats

“…A spontaneous alternation was defined as any combination of three sequential entries in which the animal entered all three arms (e.g., ABC, CAB, or BCA, but not ABB). The percentage of spontaneous alternation was used as an index of working memory and calculated according to the following equation: The spontaneous alternation (%)=[(number of alternations)/(total arm entries-2)] x100( 32 ). After each session, the maze was cleaned with 70% ethanol to avoid odors.…”

Neuronal activity and remyelination: new insights into the molecular mechanisms and therapeutic advancements

“…It is reported that low intensity rTMS in an intermittent theta burst stimulation pattern upregulated oligodendrocytes survival and promoted myelination. Four weeks of daily rTMS has been demonstrated to enhance oligodendrocyte myelination in both healthy adult mice and demyelinated mice, while also reducing depression-like symptoms and facilitating cognitive recovery in demyelinated mice ( Cullen et al, 2019 ; Wang et al, 2021 ; Mooshekhian et al, 2022 ). Recently, a randomized controlled trial has been conducted to assess the safety and remyelination in multiple sclerosis patients ( Makowiecki et al, 2022 ).…”

“…Evidence suggests that controlling neuronal excitability may be an appropriate novel intervention for clinical therapy of demyelination conditions. Neuronal activity can be stimulated directly or indirectly by various methods such as optogenetics, chemogenetics, transcranial stimulation, and sensory stimulation ( Nagy et al, 2017 ; Maas and Angulo, 2021 ; Mooshekhian et al, 2022 ). In this review, we focus on recent advances in neuronal activity and remyelination, as well as the related mechanisms of neural signaling pathways.…”

Acetyl-L-carnitine Improves Depressive-like Behaviors Through Nitric Oxide Modulation in the Cuprizone Intoxication Mouse Model of Multiple Sclerosis

“…Depression, which may begin before the clinical diagnosis of MS, can significantly affect the patient's quality of life (3). Studies indicate that demyelination in the inner prefrontal cortex (PFC) and diffuse white matter (WM), such as the corpus callosum (CC), is associated with increased depressive-like behaviors (4,5). Additionally, the activation of neuroinflammatory agents and the increase of free radicals, such as nitric oxide (NO), which in turn induces further inflammatory responses, occur in patients with depression (6).…”