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Essential role of brain-derived neurotrophic factor in adult hippocampal function.


ABSTRACT: Brain-derived neurotrophic factor (BDNF) regulates neuronal development and function. However, it has been difficult to discern its role in the adult brain in influencing complex behavior. Here, we use a recently developed inducible knockout system to show that deleting BDNF in broad forebrain regions of adult mice impairs hippocampal-dependent learning and long-term potentiation. We use the inducible nature of this system to show that the loss of BDNF during earlier stages of development causes hyperactivity and more pronounced hippocampal-dependent learning deficits. We also demonstrate that the loss of forebrain BDNF attenuates the actions of desipramine, an antidepressant, in the forced swim test, suggesting the involvement of BDNF in antidepressant efficacy. These results establish roles for BDNF in the adult, and demonstrate the strength of this inducible knockout system in studying gene function in the adult brain.

SUBMITTER: Monteggia LM 

PROVIDER: S-EPMC490019 | biostudies-literature | 2004 Jul

REPOSITORIES: biostudies-literature

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Essential role of brain-derived neurotrophic factor in adult hippocampal function.

Monteggia Lisa M LM   Barrot Michel M   Powell Craig M CM   Berton Olivier O   Galanis Victor V   Gemelli Terry T   Meuth Sven S   Nagy Andreas A   Greene Robert W RW   Nestler Eric J EJ  

Proceedings of the National Academy of Sciences of the United States of America 20040712 29


Brain-derived neurotrophic factor (BDNF) regulates neuronal development and function. However, it has been difficult to discern its role in the adult brain in influencing complex behavior. Here, we use a recently developed inducible knockout system to show that deleting BDNF in broad forebrain regions of adult mice impairs hippocampal-dependent learning and long-term potentiation. We use the inducible nature of this system to show that the loss of BDNF during earlier stages of development causes  ...[more]

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