MIP 2�� overexpression actually enhanced caveolin 1 levels. Activation of cAMP dependent signaling path ways using dBcAMP or application of TGF can reduce the expression of caveolin 1 and increase GLT 1 expres sion in rat astrocytes, suggesting a reciprocal regula tion of the two proteins in primary astrocytes. Excessive glutamate stimulation full report is excitotoxic to neurons, and astrocytes protect against glutamate neurotoxicity by removing extracellular glutamate via glutamate transporter activity. The overexpression of MIP 2�� by astrocytes down regulated GLT 1 expres sion and reduced glutamate uptake. We found pharmacological inhibitors, specifically PDTC, LY294002, KT5720 inhibi tor and PD98059 blocked MIP 2�� mediated changes in GLT 1 expression.

Taken together, these results support the hypothesis that MIP 2�� decreases GLT 1 activity in astrocytes through NF ��B, Inhibitors,Modulators,Libraries PKA, PI3K, and partly through MEK ERK signal transduction pathways. We used two model systems to evaluate whether MIP 2�� overexpression changed glutamate neurotox icity. The first, a co culture of astrocytes and neurons, models their interaction to modulate effects of Inhibitors,Modulators,Libraries glutam ate. Neurons withdrawn from co culture with MIP 2�� transduced astrocytes were more sensitive to glutamate toxicity than mock transduced cells. The second model involves use of conditioned medium from astrocytes, which did not alter neuronal sensitivity to glutamate toxicity. These results suggest that MIP 2�� itself is not toxic, but that the enhanced neuronal sensitivity to excitotoxicity was caused by the decreased GLT 1 ac tivity induced by MIP 2��.

In conclusion, chemokines and their receptors Inhibitors,Modulators,Libraries are primarily involved Inhibitors,Modulators,Libraries in regulating CNS inflammatory pro cesses. MIP 2�� may provide a new pathway for neuron glia Inhibitors,Modulators,Libraries communications that are relevant to both normal brain function and neuroinflammatory and neurodegen erative diseases. Furthermore, this research should reveal the potential utility of chemokines and their receptors as targets for therapeutic intervention in CNS disease.
Background Microglia are the prime immune effector cells of the central nervous system. The origin, morphology and role of microglia in health and disease were first elaborately described in 1939. The amoeboid micro glial cells, which are abundant in the periven tricular white matter, namely the corpus callosum of the brain function as macrophages in the developing brain.

Studies have demonstrated that AMC gradually transform into ramified microglial cells with ad vancing age. The time course of development of microglia differs in different regions of the brain. In the CC, AMC pre ponderate a week before birth in mice and rats and actively phagocytose the cellular debris and refine axonal connectivity during the first postnatal 17-AAG supplier week.