Effects of Low Field Magnetic Stimulation on
Date
2020-10-05
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
0000-0002-2190-2818
Type
Thesis
Degree Level
Masters
Abstract
Cognitive 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.
Description
Keywords
Demyelination, Multiple Sclerosis, Cuprizone, Cognitive deficit
Citation
Degree
Master of Science (M.Sc.)
Department
Psychiatry
Program
Health Sciences