n-3 polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism.
Decreased docosahexaenoic acid (DHA) and brain-derived neurotrophic factor (BDNF) have been implicated in bipolar disorder. It also has been reported that dietary deprivation of n-3 polyunsaturated fatty acids (PUFAs) for 15 weeks in rats, increased their depression and aggression scores. Here, we show that n-3 PUFA deprivation for 15 weeks decreased the frontal cortex DHA level and reduced frontal cortex BDNF expression, cAMP response element binding protein (CREB) transcription factor activity and p38 mitogen-activated protein kinase (MAPK) activity. Activities of other CREB activating protein kinases were not significantly changed. The addition of DHA to rat primary cortical astrocytes in vitro, induced BDNF protein expression and this was blocked by a p38 MAPK inhibitor. DHA's ability to regulate BDNF via a p38 MAPK-dependent mechanism may contribute to its therapeutic efficacy in brain diseases having disordered cell survival and neuroplasticity.
Rao
J S
JS
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. jrao@mail.nih.gov
Ertley
R N
RN
Lee
H-J
HJ
DeMar
J C
JC
Arnold
J T
JT
Rapoport
S I
SI
Bazinet
R P
RP
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001714:Bipolar Disorder / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000201:enzymology; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D005625:Frontal Lobe / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; C508137:Creb1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D004042:Dietary Fats, Unsaturated; D004791:Enzyme Inhibitors; D015525:Fatty Acids, Omega-3; D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole