Eicosapentaenoic acid stimulates the expression of myelin proteins in rat brain.
We have previously demonstrated that, in C6 glioma cells, eicosapentaenoic acid (EPA) stimulates the expression of proteolipid protein (PLP) via cAMP-mediated pathways. In this study, we investigated whether n-3 polyunsaturated fatty acids can affect myelinogenesis in vivo. A single dose of either EPA or docosahexaenoic acid (DHA) was injected intracerebroventricularly into 2-day-old rats, which were then killed after 3 days post-injection (p.i.). Total RNA was isolated from the medulla, cerebellum, and cortex, and the expression of myelin-specific mRNAs was analyzed by real-time PCR. The levels of PLP, myelin basic protein, and myelin oligodendrocyte protein mRNAs increased in nearly all brain regions of DHA- and EPA-treated animals, but the effect was more pronounced in EPA-treated rats. The enhancement in PLP transcript levels was followed by an increase in PLP translation in EPA-treated rats. A further indicator of accelerated myelination was the increase in 2'-3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) protein levels. In EPA-treated rats, the increased expression of myelin genes coincided with a decrease of cAMP-response element-binding protein (CREB)-DNA binding in the cerebellum and cortex (1 hr p.i.). After 16 hr, this effect was still present in the same cerebral regions even though the decrease in EPA-treated rats was less pronounced than in controls. The down-regulation of CREB activity was due to a decrease in the levels of CREB phosphorylation. In conclusion, our data suggest that EPA stimulates the expression of specific myelin proteins through decreased CREB phosphorylation. These results corroborate the clinical studies of the n-3 PUFA beneficial effects on several demyelinating diseases.
Salvati
Serafina
S
Department of Food, Nutrition and Health, Istituto Superiore di Sanità, Rome, Italy. salvatis@iss.it
Natali
Francesco
F
Attorri
Lucilla
L
Di Benedetto
Rita
R
Leonardi
Fabiana
F
Di Biase
Antonella
A
Ferri
Federica
F
Fortuna
Stefano
S
Lorenzini
Paola
P
Sanchez
Massimo
M
Ricceri
Laura
L
Vitelli
Luigi
L
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000008:administration & dosage; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D024202:Electrophoretic Mobility Shift Assay; D015870:Gene Expression / Q000187:drug effects*; D007276:Injections, Intraventricular; D009185:Myelin Proteins / Q000187:drug effects* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017362:Cyclic AMP Response Element-Binding Protein; D009185:Myelin Proteins; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid