title: ERK signalling pathway is not involved in PSA-NCAM-dependent alterations of hippocampal plasticity evoked by CB1 receptor activation.
abstract: The present study investigated the potential role of the extracellular signal-regulated kinase (ERK) pathway in the alternation of polysialylated neural cell adhesion molecule (PSA-NCAM) expression and proliferation rates in the dentate gyrus (DG) evoked by activation of the CB1 receptor. When given at a dose of 0.1 mg/kg, the CB1 receptor agonist, 3-(1,1-dimethylheptyl)-11-hydroxy-Delta(8)-tetrahydrocannabinol (HU-210), increased the levels of the phosphorylated forms of ERK (pERK1 and pERK2) in the hippocampus when measured 30 min after injection. This HU-210-induced effect was inhibited by alpha-{amino[(4-aminophenyl)thio]methylene}-2-(trifluoromethyl) benzeneacetonitrile (SL327, 30 mg/kg) - an inhibitor of mitogen-activated protein kinase kinase (MEK1/2), the upstream kinase of ERK - given 1 h before HU-210 administration. Additionally, SL327 alone significantly attenuated the basal level of both pERK1 and pERK2. HU-210 (0.1 mg/kg) decreased the number of PSA-NCAM-immunoreactive (IR) cells but did not affect the rate of proliferation, which was analyzed as the number of Ki-67-IR cells measured in the DG 2 days after HU-210 administration. The data indicated that SL327 (30 mg/kg) alone decreased the number of PSA-NCAM-IR cells 2 days after treatment. Joint administration of SL327 and HU-210 decreased the number of PSA-NCAM cells more robustly than did the administration of either alone. In addition, SL327 did not decrease the number of Ki-67-IR cells, while pretreatment with SL327 1 h before HU-210 administration did. These results suggest that stimulation of the ERK cascade caused by CB1 receptor activation is not involved in hippocampal plasticity governed by PSA-NCAM expression.
authors.affiliation: Laboratory of Pharmacology and Brain Biostructure, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. mackow@if-pan.krakow.pl
authors.forename: Marzena
authors.initials: M
authors.lastname: Maćkowiak
authors.forename: Dorota
authors.initials: D
authors.lastname: Dudys
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Wedzony
mesh_terms: D000607:Aminoacetonitrile / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D018891:Dentate Gyrus / Q000378:metabolism; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D015870:Gene Expression; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D009473:Neuronal Plasticity; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019394:Ki-67 Antigen; D039842:Neural Cell Adhesion Molecule L1; D043884:Receptor, Cannabinoid, CB1; C424127:SL 327; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D000607:Aminoacetonitrile; D013759:Dronabinol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C062018:HU 211