|Ph.D Student||Ben-Yakir Blumkin Moria|
|Subject||The Neuroprotective Effect of Magnetic Fields in Primary|
Neuronal Cultures and in Vivo:
Charactreization and Mechanism of Action
|Department||Department of Medicine||Supervisors||Professor Emeritus John Finberg|
|Professor Levi Schachter|
|Full Thesis text|
Low intensity magnetic fields (MFs) have been shown to exert beneficial effects on various biological tissues, and are currently in use mainly for the treatment of pain and inflammatory conditions. In the central nervous system (CNS), MFs have been reported to affect myriad biological functions and regulate cell fate by influencing gene expression, cell proliferation and differentiation, and apoptosis. The application of static fields (SMFs) on charged particles may affect their trajectory. A growing number of studies have been suggesting the potential role of Ca2 homeostasis and transport in mediating the beneficial effects of magnetic fields on cells, and several theoretical models aimed at explaining the physical interaction of MFs with ions have been formulated. In this work, we studied the effect of low intensity (50 Gauss) SMFs in cultured primary neuronal cultures, and established a dual defensive action exerted these fields, involving both the defense against neurotoxin-induced apoptosis, and the stimulation of the genesis of new neurons in primary cortical cultures. We show that SMFs provide neuroprotection that is related to their anti-apoptotic capacity, which is mediated by Ca2 influx through voltage gated calcium channels (VGCCs). The anti-apoptotic protection against neurotoxin-induced apoptosis provided by SMFs is dose- and time -dependent, and involves both the stabilization of the mitochondrial membrane potential and a decrease in the expression of pro-apoptotic proteins. Moreover, we show that SMFs promote neuronal survival by stimulating neurogenesis in cortical neurons (in vitro), as well as in the sub-ventricular zone in rats (in vivo). In cortical neurons, neurogenesis was associated with enhanced expression of pro-neurogenic bHLH genes and the activation of the Wnt-signaling pathway, a route tightly involved in the regulation of developmental as well as adult neurogenesis. SMF-exposed cortical neurons express higher levels of BDNF and TrkB, which are both regulated by Ca2 influx through L-type VGCCs. The involvement of L-type VGCCs in the response of cortical neurons to SMFs indicates a role for Ca2 influx through these specific channels, that may mediate the observed alterations in the relative expression of TrkB isoforms that activate BDNF-related pro-survival pathway.
In light of the massive death of neurons occurring in neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease and the association of apoptosis with the dysfunction and death of these neurons, the identification of agents that reduce the extent of neuronal apoptosis and promote neuronal plasticity may lead to development of new strategies for treating neurodegenerative disorders.