Original ArticleSelective Loss of Brain-Derived Neurotrophic Factor in the Dentate Gyrus Attenuates Antidepressant Efficacy
Section snippets
Floxed BDNF Mice
The floxed BDNF mice have previously been described (32). In prior studies, we crossed these floxed BDNF mice with a neuron-specific enolase (NSE)–tetracycline transactivator (tTA) × tetracycline operator sequences (TetOp)–Cre line to create an inducible deletion of BDNF in the brain as well as a targeted deletion of BDNF in the ventral tegmental area (28, 31). These studies demonstrated that BDNF is only deleted in the presence of Cre recombinase in the floxed mice. For the present study, only
Localized Regional Specific Deletion of BDNF in Hippocampus
We generated a localized selective deletion of the BDNF gene in the CA1 or DG with a floxed BDNF mouse, in which exon 6, the single coding region of the BDNF gene, is flanked by loxP sites (32). The BDNF floxed mice were bilaterally injected with AAV-Cre into CA1 or DG to induce the localized KO. We have previously demonstrated that this AAV-Cre construct mediates recombination in the brain after injection into BDNF floxed mice (31). As a control, floxed BDNF mice received bilateral injections
Discussion
Results of this study demonstrate that the loss of BDNF selectively in the DG results in an attenuation of antidepressant efficacy. In contrast, the selective loss of BDNF in the CA1 subregion of the hippocampus did not alter the response to antidepressants. Mice with a selective loss of BDNF in either the CA1 or DG region of the hippocampus have normal locomotor activity, anxiety-like behavior, fear-conditioning, and depression-like behavior. These data suggest that the loss of BDNF in either
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