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  1. Article: Brain-derived neurotrophic factor conditional knockouts show gender differences in depression-related behaviors.

    Monteggia, Lisa M / Luikart, Bryan / Barrot, Michel / Theobold, David / Malkovska, Irena / Nef, Serge / Parada, Luis F / Nestler, Eric J

    Biological psychiatry

    2007  Volume 61, Issue 2, Page(s) 187–197

    Abstract: Background: Indirect evidence suggests that loss of brain-derived neurotrophic factor (BDNF) from forebrain regions contributes to an individual's vulnerability for depression, whereas upregulation of BDNF in these regions is suggested to mediate the ... ...

    Abstract Background: Indirect evidence suggests that loss of brain-derived neurotrophic factor (BDNF) from forebrain regions contributes to an individual's vulnerability for depression, whereas upregulation of BDNF in these regions is suggested to mediate the therapeutic effect of antidepressants.
    Methods: We have tested this hypothesis by generating two independent lines of conditional BDNF knockout mice in which the BDNF gene is deleted selectively in forebrain.
    Results: We show that male conditional knockouts exhibit hyperactivity but normal depression-related behaviors. In contrast, female conditional knockouts display normal locomotor activity but a striking increase in depression-like behavior. We also demonstrate that loss of BDNF in both male and female mice attenuates the actions of the antidepressant desipramine in the forced swim test.
    Conclusions: These gender differences in depression-related behaviors in BDNF conditional knockout mice provide direct evidence for a role of BDNF in depression. The results also support the view that forebrain BDNF may be essential in mediating antidepressant efficacy.
    MeSH term(s) Alleles ; Animals ; Antidepressive Agents, Tricyclic/pharmacology ; Anxiety Disorders/genetics ; Brain-Derived Neurotrophic Factor/genetics ; Depressive Disorder/genetics ; Desipramine/pharmacology ; Female ; Male ; Mice ; Mice, Knockout ; Motor Activity/physiology ; Prosencephalon/pathology ; RNA, Messenger/genetics ; Sex Factors ; Stress, Psychological/complications
    Chemical Substances Antidepressive Agents, Tricyclic ; Brain-Derived Neurotrophic Factor ; RNA, Messenger ; Desipramine (TG537D343B)
    Language English
    Publishing date 2007-01-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2006.03.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article: Mania-like behavior induced by disruption of CLOCK.

    Roybal, Kole / Theobold, David / Graham, Ami / DiNieri, Jennifer A / Russo, Scott J / Krishnan, Vaishnav / Chakravarty, Sumana / Peevey, Joseph / Oehrlein, Nathan / Birnbaum, Shari / Vitaterna, Martha H / Orsulak, Paul / Takahashi, Joseph S / Nestler, Eric J / Carlezon, William A / McClung, Colleen A

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

    2007  Volume 104, Issue 15, Page(s) 6406–6411

    Abstract: Circadian rhythms and the genes that make up the molecular clock have long been implicated in bipolar disorder. Genetic evidence in bipolar patients suggests that the central transcriptional activator of molecular rhythms, CLOCK, may be particularly ... ...

    Abstract Circadian rhythms and the genes that make up the molecular clock have long been implicated in bipolar disorder. Genetic evidence in bipolar patients suggests that the central transcriptional activator of molecular rhythms, CLOCK, may be particularly important. However, the exact role of this gene in the development of this disorder remains unclear. Here we show that mice carrying a mutation in the Clock gene display an overall behavioral profile that is strikingly similar to human mania, including hyperactivity, decreased sleep, lowered depression-like behavior, lower anxiety, and an increase in the reward value for cocaine, sucrose, and medial forebrain bundle stimulation. Chronic administration of the mood stabilizer lithium returns many of these behavioral responses to wild-type levels. In addition, the Clock mutant mice have an increase in dopaminergic activity in the ventral tegmental area, and their behavioral abnormalities are rescued by expressing a functional CLOCK protein via viral-mediated gene transfer specifically in the ventral tegmental area. These findings establish the Clock mutant mice as a previously unrecognized model of human mania and reveal an important role for CLOCK in the dopaminergic system in regulating behavior and mood.
    MeSH term(s) Analysis of Variance ; Animals ; Behavioral Symptoms/genetics ; Bipolar Disorder/drug therapy ; Bipolar Disorder/genetics ; Bipolar Disorder/pathology ; Bipolar Disorder/therapy ; CLOCK Proteins ; Circadian Rhythm/genetics ; Electric Stimulation ; Gene Expression Regulation/genetics ; Gene Transfer Techniques ; Genetic Therapy/methods ; Glycogen Synthase Kinase 3/genetics ; Glycogen Synthase Kinase 3 beta ; Immunohistochemistry ; Lithium/pharmacology ; Lithium/therapeutic use ; Lithium Compounds/pharmacology ; Lithium Compounds/therapeutic use ; Locomotion/drug effects ; Mice ; Mutagenesis ; Mutation/genetics ; Trans-Activators/genetics ; Trans-Activators/therapeutic use ; Ventral Tegmental Area/drug effects
    Chemical Substances Lithium Compounds ; Trans-Activators ; Lithium (9FN79X2M3F) ; CLOCK Proteins (EC 2.3.1.48) ; CLOCK protein, human (EC 2.3.1.48) ; Clock protein, mouse (EC 2.3.1.48) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Glycogen Synthase Kinase 3 (EC 2.7.11.26)
    Language English
    Publishing date 2007-03-22
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.0609625104
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1148: Show issues Location:
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  3. Article: Mania-like behavior induced by disruption of CLOCK

    Roybal, Kole / Theobold, David / Graham, Ami / DiNieri, Jennifer A / Russo, Scott J / Krishnan, Vaishnav / Chakravarty, Sumana / Peevey, Joseph / Oehrlein, Nathan / Birnbaum, Shari / Vitaterna, Martha H / Orsulak, Paul / Takahashi, Joseph S / Nestler, Eric J / Carlezon, William A. Jr / McClung, Colleen A

    Proceedings of the National Academy of Sciences of the United States of America. 2007 Apr. 10, v. 104, no. 15

    2007  

    Abstract: Circadian rhythms and the genes that make up the molecular clock have long been implicated in bipolar disorder. Genetic evidence in bipolar patients suggests that the central transcriptional activator of molecular rhythms, CLOCK, may be particularly ... ...

    Abstract Circadian rhythms and the genes that make up the molecular clock have long been implicated in bipolar disorder. Genetic evidence in bipolar patients suggests that the central transcriptional activator of molecular rhythms, CLOCK, may be particularly important. However, the exact role of this gene in the development of this disorder remains unclear. Here we show that mice carrying a mutation in the Clock gene display an overall behavioral profile that is strikingly similar to human mania, including hyperactivity, decreased sleep, lowered depression-like behavior, lower anxiety, and an increase in the reward value for cocaine, sucrose, and medial forebrain bundle stimulation. Chronic administration of the mood stabilizer lithium returns many of these behavioral responses to wild-type levels. In addition, the Clock mutant mice have an increase in dopaminergic activity in the ventral tegmental area, and their behavioral abnormalities are rescued by expressing a functional CLOCK protein via viral-mediated gene transfer specifically in the ventral tegmental area. These findings establish the Clock mutant mice as a previously unrecognized model of human mania and reveal an important role for CLOCK in the dopaminergic system in regulating behavior and mood.
    Language English
    Dates of publication 2007-0410
    Size p. 6406-6411.
    Publishing place National Academy of Sciences
    Document type Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    Database NAL-Catalogue (AGRICOLA)

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