Zhang, Yanbo2020-10-052020-10-052019-092020-10-05Septemberhttp://hdl.handle.net/10388/13084Cognitive impairment (CI) is a leading cause of disability in patients with Multiple Sclerosis (MS). Although CI has catastrophic effects on patients’ quality of life, there is no approved treatment for it. Low Field Magnetic Stimulation (LFMS) is a novel non-invasive brain stimulation technique that has promising benefits in improving mood and cognitive function in animal studies of traumatic brain injury, major depressive disorder and Alzheimer’s disease, suggesting a transtherapeutic cognitive benefit among different neuropsychiatric disorders. In this study, we hypothesized that LFMS can alleviate demyelination-related cognitive deficits in a cuprizone (CPZ) mouse model of MS. CPZ is a copper chelator widely used to generate brain demyelination. Feeding CPZ to young adult mice for six weeks generates diffuse demyelinating lesions in both gray matter and white matter areas, predominantly in the prefrontal cortex, hippocampus and corpus callosum. One-hundred and twenty mice were divided into four groups (30 mice/group) and received CPZ (no, yes) and LFMS (no, yes) for up to 6 weeks, respectively. Behavioral tests including open-field test (OFT), Y-maze test and forced swim test (FST) were done after 3 and 6 weeks of treatment. Half of the mice from each group were euthanized at each time point, followed by brain immunobiology and Western blots. The study showed that CPZ treatment caused significant working memory, short term memory and learning deficits, which were prevented with LFMS co-administration. The OFT and Y-maze test did not reveal motor function impairment in demyelinated mice. LFMS treatment also decreased the severity of demyelination in both frontal cortex and hippocampus. LFMS may exert its protective effects through modulating the expression of Transforming ii i Growth Factor Beta-1 (TGF-β1), a target for an investigational intervention under clinical trials for MS. TGF-β1 is a critical cytokine for neurogenesis and inflammation. The results suggest the therapeutic potential of LFMS for cognitive remediation in MS patients. In addition, it provides a non-invasive and affordable approach to increase TGF-β1 in the brain for neuroprotection and neurogenesis.application/pdfDemyelinationMultiple SclerosisCuprizoneCognitive deficitThesis2020-10-05