Microglia are known to be exquisite sensors of even minor pathological changes in the CNS. They also act as active contributors to neuronal damage in neurodegenerative diseases such as Alzheimers disease, Parkinsons disease and HIV dementia. An increasing amount of evidence suggests that migroglia are key factors in the clearly process of neuroinflammation. Microglia induced neuronal injury may be mediated by the production of TNF a, NO, and reactive oxygen species. Our results confirm significant up regulation of TNF a and iNOS mRNA, and release of the pro inflammatory factors TNF a and NO, in N9 microglia after EMF exposure. These results suggest that EMF, as an external physical factor, could facilitate microglia pro inflammatory responses through the secretion of pro inflammatory factors.

This activity may ultimately contribute Inhibitors,Modulators,Libraries to CNS impairment or disease. It is well known that microglia monitor the external environment and respond to external stimuli via signaling cascades that allow them to perturb mem brane function and trigger the activation of one or more intracellular signaling pathways. In contrast, there is a lack of information regarding signal transduction mechanisms and molecular targets of EMF activated microglia. Here, our time course experiments show dif ferent expression levels of the JAK STAT pathway in EMF activated microglia. It has been demonstrated that the JAK STAT cascade plays an essential role in driving a variety of immune responses in glial cells in the brain.

Different expression levels of the JAK STAT pathway have been detected in glial cells in the brain and associated with pathological CNS conditions such as cerebral ischemia, trau matic brain injury and brain inflammation. These observations suggest that EMF exposure Inhibitors,Modulators,Libraries likely affects microglial activation through the activation of the JAK STAT pathway. To investigate the potential function of the JAK STAT pathway in EMF activated microglia, we next examined whether the JAK inhibitor P6 could affect the EMF induced increases of TNF a, iNOS, NO and CD11b. P6 can effectively block the activation of JAK1, JAK2 and STAT3. Our results revealed that the activation of JAK2 increased with kinetics Inhibitors,Modulators,Libraries similar to those of phos phorylated STAT3. The activation of JAK2 and STAT3 was significantly inhibited by P6 at 3 and 12 h after EMF exposure.

These results provide further evidence Inhibitors,Modulators,Libraries that JAK2 STAT3 signaling plays a role in the reactivity of EMF stimulated microglia. Most previous studies have shown that the JAK STAT signaling pathway is involved in microglial activation. Inhibitors,Modulators,Libraries In our study, the activation of microglia, http://www.selleckchem.com/products/Cisplatin.html the transcription of TNF a and iNOS, and the secretion of TNF a and NO were not significantly inhibited at 3 h by P6 in EMF activated microglia, however. These results suggest that the JAK2 STAT3 pathway may not mediate the initial activation of microglia after EMF exposure.