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The galanin‐R2 agonist AR‐M1896 reduces glutamate toxicity in primary neural hippocampal cells
Author(s) -
Pirondi Stefania,
Fernandez Mercedes,
Schmidt Ralf,
Hökfelt Tomas,
Giardino Luciana,
Calzà Laura
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03437.x
Subject(s) - glutamate receptor , galanin , glutamatergic , galanin receptor , agonist , excitotoxicity , hippocampal formation , neuropeptide , biology , toxicity , receptor , medicine , chemistry , endocrinology , biochemistry
Galanin is a neuropeptide involved in a variety of biological functions, including having a strong anticonvulsant activity. To assess a possible role of galanin in modulation of glutamatergic synapses and excitotoxicity, we studied effects of a galanin receptor 2(3) agonist (AR‐M1896) on several molecular events induced by glutamate administration in primary neural hippocampal cells. Exposure of cells, after 5 days in vitro, to glutamate 0.5 m m for 10 min caused morphological alterations, including disaggregation of β‐tubulin and MAP‐2 cytoskeletal protein assembly, loss of neurites and cell shrinkage. When present in culture medium together with glutamate, 1 and 10 n m of AR‐M1896 reduced these alterations. Moreover, AR‐M1896 counteracted glutamate‐induced c‐ fos mRNA and c‐Fos protein up‐regulation after 30–150 min, and 24 h, respectively. Massive nuclear alterations (Hoechst 33258 staining), observed 24 h after glutamate exposure, were also antagonized by AR‐M1896 (0.1–100 n m ) in a dose‐dependent manner. These findings indicate that galanin, probably mainly through its type 2 receptor, interferes with events associated with glutamate toxicity.