Neuronal release of vasoactive intestinal peptide is important to astrocytic protection of neurons from glutamate toxicity

Astrocytes regulate clearance of glutamate from the vicinity of neurons. This helps to protect neurons directly from glutamate toxicity. Recent findings have indicated that a complex molecular interaction between neurons and astrocytes that is necessary for this protection occurs. In the present investigation the role of vasoactive intestinal peptide (VIP) in signaling between neurons and astrocytes was investigated. VIP was found to be necessary for the protective effects of astrocytes in a coculture system. VIP in combination with neuronal-conditioned medium enhanced glutamate uptake by astrocytes. Also, VIP enhanced the expression of the high-affinity VIP receptor, increased astrocytic release of interleukin-6, and indirectly reduced the toxicity of glutamate in neuronal-conditioned astrocyte medium. These results indicate that VIP is essential to the molecular interaction of neurons and astrocytes and is involved in the regulation of the protective effects of astrocytes for neurons.