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n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

A Retraction to this article was published on 26 September 2017

Abstract

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.

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Abbreviations

BDNF:

brain derived neurotrophic factor

CaMK:

Ca2+ calmodulin kinase

CREB:

cAMP response element binding protein

DHA:

docosahexaenoic acid

GFAP:

glial fibrillary acidic protein

MAPK:

mitogen activated protein kinase

MBP:

myelin basic protein

PUFA:

polyunsaturated fatty acid

PKA:

protein kinase A

PKC:

protein kinase C

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Acknowledgements

This work was entirely supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. We thank Drs Christopher Toscano and Sang-Ho Choi for assistance with the florescence microscopy.

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Rao, J., Ertley, R., Lee, HJ. et al. n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism. Mol Psychiatry 12, 36–46 (2007). https://doi.org/10.1038/sj.mp.4001888

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