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The glial cell line-derived neurotrophic factor (GDNF) was first identified as a survival factor for midbrain dopaminergic neurons, but additional studies provided evidences for a role as a trophic factor for other neurons of the central and peripheral nervous systems. GDNF regulates cellular activity through interaction with glycosyl-phosphatidylinositol-anchored cell surface receptors, GDNF family receptor-α1, which might signal through the transmembrane Ret tyrosine receptors or the neural cell adhesion molecule, to promote cell survival, neurite outgrowth, and synaptogenesis. The neuroprotective effect of exogenous GDNF has been shown in different experimental models of focal and global brain ischemia, by local administration of the trophic factor, using viral vectors carrying the GDNF gene and by transplantation of GDNF-expressing cells. These different strategies and the mechanisms contributing to neuroprotection by GDNF are discussed in this review. Importantly, neuroprotection by GDNF was observed even when administered after the ischemic injury.

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J. Neurochem. (2009) 109, 911–922. Abstract Adrenal chromaffin cells synthesize and secrete catecholamines and neuropeptides that may regulate hormonal and paracrine signaling in stress and also during inflammation. The aim of our work was to study the role of the cytokine interleukin‐1β (IL‐1β) on catecholamine release and synthesis from primary cell cultures of human adrenal chromaffin cells. The effect of IL‐1β on neuropeptide Y (NPY) release and the intracellular pathways involved in catecholamine release evoked by IL‐1β and NPY were also investigated. We observed that IL‐1β increases the release of NPY, norepinephrine (NE), and epinephrine (EP) from human chromaffin cells. Moreover, the immunoneutralization of released NPY inhibits catecholamine release evoked by IL‐1β. Moreover, IL‐1β regulates catecholamine synthesis as the inhibition of tyrosine hydroxylase decreases IL‐1β‐evoked catecholamine release and the cytokine induces tyrosine hydroxylase Ser40 phosphorylation. Moreover, IL‐1β induces catecholamine release by a mitogen‐activated protein kinase (MAPK)‐dependent mechanism, and by nitric oxide synthase activation. Furthermore, MAPK, protein kinase C (PKC), protein kinase A (PKA), and nitric oxide (NO) production are involved in catecholamine release evoked by NPY. Using human chromaffin cells, our data suggest that IL‐1β, NPY, and nitric oxide (NO) may contribute to a regulatory loop between the immune and the adrenal systems, and this is relevant in pathological conditions such as infection, trauma, stress, or in hypertension.

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