The galanin-R2 agonist AR-M1896 reduces glutamate toxicity in primary neural hippocampal cells.
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 mM for 10 min caused morphological alterations, including disaggregation of beta-tubulin and MAP-2 cytoskeletal protein assembly, loss of neurites and cell shrinkage. When present in culture medium together with glutamate, 1 and 10 nM 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 nM) in a dose-dependent manner. These findings indicate that galanin, probably mainly through its type 2 receptor, interferes with events associated with glutamate toxicity.
Pirondi
Stefania
S
Department of Veterinary Morphophysiology and Animal Production, University of Bologna, Bologna, Italy.
Fernandez
Mercedes
M
Schmidt
Ralf
R
Hökfelt
Tomas
T
Giardino
Luciana
L
Calzà
Laura
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D019004:Galanin / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D011247:Pregnancy; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044092:Receptor, Galanin, Type 2 / Q000819:agonists*; D014404:Tubulin / Q000378:metabolism
D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D044092:Receptor, Galanin, Type 2; D014404:Tubulin; C434734:galanin (2-11)-amide; D018698:Glutamic Acid; D019004:Galanin