title: Galanin acts as a neuroprotective factor to the hippocampus.
abstract: The expression of the neuropeptide galanin is markedly up-regulated in many areas of the central and peripheral nervous system after injury. We have recently demonstrated that peripheral sensory neurons depend on galanin for neurite extension after injury, mediated by activation of the second galanin receptor subtype (GALR2). We therefore hypothesized that galanin might also act in a similar manner in the CNS, reducing cell death in hippocampal models of excitotoxicity. Here we report that galanin acts an endogenous neuroprotective factor to the hippocampus in a number of in vivo and in vitro models of injury. Kainate-induced hippocampal cell death was greater in both the CA1 and CA3 regions of galanin knockout animals than in WT controls. Similarly, exposure to glutamate or staurosporine induced significantly more neuronal cell death in galanin knockout organotypic and dispersed primary hippocampal cultures than in WT controls. Conversely, less cell death was observed in the hippocampus of galanin overexpressing transgenic animals after kainate injection and in organotypic cultures after exposure to staurosporine. Further, exogenous galanin or the previously described high-affinity GALR2 agonist, both reduced cell death when coadministered with glutamate or staurosporine in WT cultures. These results demonstrate that galanin acts an endogenous neuroprotective factor to the hippocampus and imply that a galanin agonist might have therapeutic uses in some forms of brain injury.
authors.affiliation: Laboratories for Integrative Neuroscience and Endocrinology, Bristol University, Whitson Street, Bristol BS1 3NY, United Kingdom.
authors.forename: Caroline R
authors.initials: CR
authors.lastname: Elliott-Hunt
authors.forename: Barnaby
authors.initials: B
authors.lastname: Marsh
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacon
authors.forename: Robert
authors.initials: R
authors.lastname: Pope
authors.forename: Penny
authors.initials: P
authors.lastname: Vanderplank
authors.forename: David
authors.initials: D
authors.lastname: Wynick
mesh_terms: D000818:Animals; D016923:Cell Death; D019004:Galanin / Q000494:pharmacology / Q000502:physiology*; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D018698:Glutamic Acid; D019004:Galanin; D019311:Staurosporine