PMID- 16983391 OWN - NLM STAT- MEDLINE DCOM- 20070227 LR - 20231213 IS - 1359-4184 (Print) IS - 1359-4184 (Linking) VI - 12 IP - 1 DP - 2007 Jan TI - n-3 polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism. PG - 36-46 AB - 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. FAU - Rao, J S AU - Rao JS AD - Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. jrao@mail.nih.gov FAU - Ertley, R N AU - Ertley RN FAU - Lee, H-J AU - Lee HJ FAU - DeMar, J C Jr AU - DeMar JC Jr FAU - Arnold, J T AU - Arnold JT FAU - Rapoport, S I AU - Rapoport SI FAU - Bazinet, R P AU - Bazinet RP LA - eng GR - Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Retracted Publication DEP - 20060919 PL - England TA - Mol Psychiatry JT - Molecular psychiatry JID - 9607835 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Creb1 protein, rat) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Dietary Fats, Unsaturated) RN - 0 (Enzyme Inhibitors) RN - 0 (Fatty Acids, Omega-3) RN - 0 (Imidazoles) RN - 0 (Pyridines) RN - 0 (RNA, Messenger) RN - 25167-62-8 (Docosahexaenoic Acids) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - PVX798P8GI (4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole) SB - IM RIN - Mol Psychiatry. 2018 Sep;23(9):1968. PMID: 28948969 MH - Animals MH - Astrocytes/cytology/metabolism MH - Bipolar Disorder/*metabolism MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Cell Nucleus/enzymology MH - Cells, Cultured MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Dietary Fats, Unsaturated/pharmacology MH - Docosahexaenoic Acids/metabolism MH - Enzyme Inhibitors/pharmacology MH - Fatty Acids, Omega-3/*pharmacology MH - Female MH - Frontal Lobe/cytology/growth & development/*metabolism MH - Imidazoles/pharmacology MH - Male MH - Phosphorylation MH - Pyridines/pharmacology MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Long-Evans MH - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism EDAT- 2006/09/20 09:00 MHDA- 2007/02/28 09:00 CRDT- 2006/09/20 09:00 PHST- 2006/09/20 09:00 [pubmed] PHST- 2007/02/28 09:00 [medline] PHST- 2006/09/20 09:00 [entrez] AID - 4001888 [pii] AID - 10.1038/sj.mp.4001888 [doi] PST - ppublish SO - Mol Psychiatry. 2007 Jan;12(1):36-46. doi: 10.1038/sj.mp.4001888. Epub 2006 Sep 19.