title: 2-Decenoic acid ethyl ester possesses neurotrophin-like activities to facilitate intracellular signals and increase synapse-specific proteins in neurons cultured from embryonic rat brain.
abstract: We presently found that medium-chain fatty acids (MCFAs) with 8-12 carbons and their esters facilitated activation (phosphorylation) of mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinases (ERK) 1/2 of cultured embryonic cortical/hippocampal neurons. In particular, trans-2-decenoic acid ethyl ester (DAEE) had the most potent activity. Additionally, DAEE activated phosphatidylinositol 3-kinase and cAMP-response element binding protein (CREB), suggesting that DAEE generates similar intracellular signal as neurotrophins. Therefore, details of the signal elicited by DAEE were examined in comparison with those of a neurotrophin, brain-derived neurotrophic factor (BDNF). We found that 1) DAEE phosphorylated MAPK/ERK1/2 via MEK activation without the involvement of tyrosine kinases of neurotrophin Trk receptors; 2) DAEE activated CREB predominantly through MAPK/ERK1/2 activation, not through other pathways such as cAMP/protein kinase A; and 3) DAEE increased the expression of RNAs of BDNF and neurotrophin-3 and the protein content of synapse-specific proteins such as synaptophysin, synapsin-1, and syntaxin. Based on these observations we propose that DAEE and some other derivatives of MCFAs having neurotrophin-like neurotrophic activities may become therapeutic tools for certain neurological or psychiatric disorders.
authors.affiliation: Laboratory of Molecular Biology, Gifu Pharmaceutical University, Daigaku-nishi 1-25-4, Gifu, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Makino
authors.forename: Munekazu
authors.initials: M
authors.lastname: Iinuma
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Fukumitsu
authors.forename: Hitomi
authors.initials: H
authors.lastname: Soumiya
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Shoei
authors.initials: S
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004622:Embryo, Mammalian; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D020933:Neurotrophin 3 / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D005229:Fatty Acids, Monounsaturated; D020933:Neurotrophin 3; D017475:Receptors, Nerve Growth Factor; C052476:2-decenoic acid; D048049:Extracellular Signal-Regulated MAP Kinases