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New insights into BDNF function in depression and anxiety

Abstract

The 'neurotrophin hypothesis of depression' is based largely on correlations between stress or antidepressant treatment and down- or upregulation, respectively, of brain-derived neurotrophic factor (BDNF). Genetic disruption of the signaling pathways involving BDNF and its receptor, the tyrosine kinase TrkB, does not seem to cause depressive behaviors, but does hamper the effect of antidepressant drugs. Thus, BDNF may be a target of antidepressants, but not the sole mediator of depression or anxiety. Advances in BDNF cell biology, including its transcription through multiple promoters, trafficking and secretion, may provide new insights into its role in mood disorders. Moreover, as the precursor proBDNF and the mature protein mBDNF can elicit opposite effects on cellular functions, the impact of proBDNF and its cleavage on mood should be considered. Opposing influences of mBDNF and proBDNF on long-term potentiation and long-term depression might contribute to the dichotomy of BDNF actions on behaviors mediated by the brain stress and reward systems.

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Acknowledgements

The authors' work is supported by funds from intramural research programs of the US National Institute of Mental Health and National Institute of Child Health and Human Development.

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Martinowich, K., Manji, H. & Lu, B. New insights into BDNF function in depression and anxiety. Nat Neurosci 10, 1089–1093 (2007). https://doi.org/10.1038/nn1971

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