Wnt-5a increases NO and modulates NMDA receptor in rat hippocampal neurons

Abstract

Wnt signaling has a crucial role in synaptic function at the central nervous system. Here we evaluate whether Wnts affect nitric oxide (NO) generation in hippocampal neurons. We found that non-canonical Wnt-5a triggers NO production; however, Wnt-3a a canonical ligand did not exert the same effect. Co-administration of Wnt-5a with the soluble Frizzled related protein-2 (sFRP-2) a Wnt antagonist blocked the NO production. Wnt-5a activates the non-canonical Wnt/Ca(2+) signaling through a mechanism that depends on Ca(2+) release from Ryanodine-sensitive internal stores. The increase in NO levels evoked by Wnt-5a promotes the insertion of the GluN2B subunit of the NMDA receptor (NMDAR) into the neuronal cell surface. To the best of our knowledge, this is the first time that Wnt-5a signaling is related to NO production, which in turn increases NMDARs trafficking to the cell surface.

Keywords: 2-bis-(o-aminophenoxy)-ethane-N,N,N′,N′tetraaceticacid,tetraacetoxymethyl ester; 7-NI; 7-nitroindazole; AraC; BAPTA-AM; BSA; CRD; Ca(2+)/calmodulin dependent kinase II; CaMKII; Calcineurin; DIV; GABA; GFAP; GluN2B subunit; JNK; N-methyl-d-aspartate receptor; NMDAR; NO; PKC; Protein phosphatase; Ryanodine receptors; SNP; Wingless-type family member 5a; Wnt-5a; Wnt/PCP; Wnt/planar cell polarity; bovine serum albumin; c-Jun N-terminal kinase; cysteine rich domain; cytosine arabinoside; days in vitro; glial fibrillary acidic protein; nNOS; neuronal NO synthase; nitric oxide; protein kinase C; sFRP-2; sodium nitroprusside dehydrate; soluble Frizzled related protein-2; γ-Aminobutiric acid.