Therefore, the effects of EMF exposure on the central nervous system have been an active topic of investigation in recent years. Sev eral studies have revealed strong glial reactivity in differ ent parts of the brain after EMF exposure. We have found activated microglia in the hippocampus and cortex of rats after exposure to EMF. In vivo animal experiments involving microglial CC 5013 activation, however, cannot clearly explain whether such activation is induced directly by EMF or indirectly as a consequence of neuronal injury from EMF exposure. Microglia, the resident innate immune cells in the CNS, become activated in response to certain cues, such as brain injury and immunological stimuli. Activated microglia undergo a dramatic morphological Inhibitors,Modulators,Libraries transformation.
They then become motile and acquire a reactive profile that is characterized by proliferation, migration and phagocytosis. Overactivated microglia can result in disastrous and progressive Inhibitors,Modulators,Libraries neu rotoxic consequences, however, leading to excess pro duction of factors such as superoxide, nitric oxide and tumor necrosis factor a that cause additional neuroinflammation. Not surprisingly, activated microglia are important in the pathogenesis of neurodegenerative diseases, such as Alzheimers disease, Parkinsons disease and amyotrophic lateral sclerosis. The signal transduction mechanisms involved in microglial activation and neuroinflammatory factors release after EMF exposure are still largely unknown. Microglia may be the principal target of the neurobiolo gical effects of EMF.
In response to extracellular stimuli, several major signaling pathways are upregulated in acti vated microglia. Several Inhibitors,Modulators,Libraries transcription factors, i. e, Inhibitors,Modulators,Libraries NF B, AP 1 and C EBP, are involved in microglial activation in vivo and in vitro. STAT signaling is another cri tical pathway that plays an important regulatory role in microglial reactivity to various stimuli, including cere bral ischemia, gangliosides, lipopolysaccharide, thrombin and cytokines. We have previously shown that the JAK STAT3 pathway is activated in EMF stimulated microglia. It is not known, however, whether JAK STAT3 signaling triggers the initial activation of EMF stimulated microglia or whether it merely participates Inhibitors,Modulators,Libraries in the pro inflammatory responses. Seliciclib clinical Recently, a JAK inhibi tor I, capable of producing complete inhibition of STAT3 activation, was shown to not alter the growth characteristics of tested cell lines even when used in a high uM range of concentrations. This obser vation suggests that persistent STAT3 inhibition with P6 may be a helpful tool in addressing the aforemen tioned questions. Imbalanced microglial activation or hyperactivation can cause neurodegeneration, but the true initial trigger of microglial activation has not been identified.