טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentUzan Gueta Ravit
SubjectNeuroprotective and Behavioral Effects of Weak Static
Magnetic Fields in the Rat
DepartmentDepartment of Medicine
Supervisor Professor Emeritus John Finberg
Full Thesis textFull thesis text - English Version


Abstract

Magnetic field’s (MF's) beneficial effect was documented over 4000 years ago, especially for analgesia. In the modern era, the use of MF as a medical treatment gained momentum in the mid-eighties with the development of transcranial magnetic stimulation (TMS), which is an accepted treatment for major depression. In addition, MFs were found to be effective in treating a variety of physiological conditions e.g. bone fractures, wound healing and pain. Accordingly many studies address MF’s effect on biological tissues as a non-invasive and innovative medical treatment for different disease conditions.

 In a previous study from our lab it was found that primary cortical neurons exposure to static magnetic field (SMF) causes a reduction in apoptosis, induced by the apoptotic agent etoposide. Accordingly we explored SMF’s neuroprotective effect on the neurodegenerative effect of 6-hydroxydopamine (6OHDA), in vivo. In addition, since TMS is commonly used for the treatment of depression, and alterations in memory and increased anxiety are observed in ageing, we studied SMF's age related effects on rat behavior, using aged rats. In addition, however, since anxiety and memory are affected by neurogenesis SMF effect on old rats neurogenic areas, was explored ,using thymidine analog, (EDU), for new neurons detection. For the study of SMF mechanism of action we used RT -PCR and RNA-sequencing, and proteomic analysis (mass spectrometry), for gene expression and protein alterations respectively.                                         

Our study demonstrated that 1 week of SMF exposure, (but not 3 or 5 weeks), caused anxiolytic effect in elderly rats, and improved recognition and spatial memory in young rats. However, SMF exposure did not affect neurogenesis in old rats' neurogenic brain areas. We also found that exposure to 6OHDA caused a reduction in dopaminergic cell number in rat substantia nigra pars compacta (SNc), however exposure to SMF protected the SNc cells from 6OHDA intoxication preserving dopaminergic cell number at normal levels. In the mechanism study, we found that SMF exposure activated anti-inflammatory and anti-apoptotic related genes and affected proteins related to cell energy and metabolism, calcium channels and myelination processes.

The results indicate that 1 week of SMF exposure exerts age dependent effects, on anxiety and memory related parameters, causing anxiolytic effect in elderly rats and improving memory in young rats. However, the anxiolytic effect observed in old rats was not correlated with neurogenesis, indicating that SMF do not affect neurogenesis in old rats' brain. Yet, a significant effect on neuronal cell survival was observed in 6OHDA-lesioned rats exposed to SMF, indicating a neuroprotective effect of SMF. Alterations in anti-inflammatory and anti-apoptotic related genes and cell metabolism, myelin related and calcium channels proteins, observed in SMF-exposed brains can partly explain SMF mechanism of action and highlights the complexity of SMF mechanisms. In general, the study indicates a possibility of using SMF for treatment of neurodegeneration and anxiety in humans.