Abstract：
:Many antidepressants stimulate adult hippocampal neurogenesis, but the mechanisms by which they increase neurogenesis and modulate behavior are incompletely understood. Here we show that hippocampal bone morphogenetic protein (BMP) signaling is modulated by antidepressant treatment, and that the changes in BMP signaling mediate effects of antidepressant treatment on neural progenitor cell proliferation and behavior. Treatment with the selective serotonin reuptake inhibitor fluoxetine suppressed BMP signaling in the adult mouse hippocampus both by decreasing levels of BMP4 ligand and increasing production of the BMP inhibitor noggin. Increasing BMP signaling in the hippocampus via viral overexpression of BMP4 blocked the effects of fluoxetine on proliferation in the dentate gyrus and on depressive behavior. Conversely, inhibiting BMP signaling via viral overexpression of noggin in the hippocampus or infusion of noggin into the ventricles exerted antidepressant and anxiolytic activity along with an increase in hippocampal neurogenesis. Similarly, conditional genetic deletion of the type II BMP receptor in Ascl1-expressing cells promoted neurogenesis and reduced anxiety- and depression-like behaviors, suggesting that neural progenitor cells contribute to the effects of BMP signaling on affective behavior. These observations indicate that BMP signaling in the hippocampus regulates depressive behavior, and that decreasing BMP signaling may be required for the effects of some antidepressants. Thus BMP signaling is a new and powerful potential target for the treatment of depression.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Brooker SM,Gobeske KT,Chen J,Peng CY,Kessler JAdoi
10.1038/mp.2016.160subject
Has Abstractpub_date
2017-06-01 00:00:00pages
910-919issue
6eissn
1359-4184issn
1476-5578pii
mp2016160journal_volume
22pub_type
杂志文章abstract：:Mental disorders cause more disability than any other class of medical illness in Americans between ages 15 and 44 years. The suicide rate is higher than the annual mortality from homicide, AIDS, and most forms of cancer. In contrast to nearly all communicable and most non-communicable diseases, there is little eviden...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/sj.mp.4001777
更新日期：2006-01-01 00:00:00
abstract：:We conducted a systematic review and meta-analysis of randomized controlled trials that compared second-generation antipsychotic (SGA) drugs with placebo in schizophrenic patients and which considered 13 different outcome measures. Thirty-eight randomized controlled trials with 7323 participants were included. All SGA...
journal_title：Molecular psychiatry
pub_type： 杂志文章,meta分析,评审
doi：10.1038/sj.mp.4002136
更新日期：2009-04-01 00:00:00
abstract：:The 102-T/C polymorphism of the 5-HT(2A) receptor gene was analysed in 159 patients with major depression and 164 unrelated and healthy controls using a case-control design. Allele and genotype frequencies did not differ between cases and controls. No differences according to sex, age of onset, melancholia, suicidal b...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000818
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-020-0695-7
更新日期：2020-02-26 00:00:00
abstract：:APAF1, encoding the protein apoptosis protease activating factor 1 (Apaf-1), has recently been established as a chromosome 12 gene conferring predisposition to major depression in humans. The molecular phenotypes of Apaf-1 variants were determined by in vitro reconstruction of the apoptosome complex in which Apaf-1 ac...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001755
更新日期：2006-01-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2017.172
更新日期：2018-05-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
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更新日期：2016-01-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2016.195
更新日期：2018-02-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
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更新日期：2013-02-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：
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journal_title：Molecular psychiatry
pub_type： 杂志文章,已发布勘误
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更新日期：2018-03-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
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更新日期：2012-10-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2012.81
更新日期：2013-05-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2017.156
更新日期：2018-11-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000771
更新日期：2000-09-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-018-0281-4
更新日期：2020-05-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2015.104
更新日期：2015-11-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2016.153
更新日期：2017-09-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-019-0356-x
更新日期：2020-04-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/mp.2016.183
更新日期：2017-02-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2016.148
更新日期：2017-05-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000711
更新日期：2000-05-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/s41380-020-00930-0
更新日期：2021-01-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-018-0232-0
更新日期：2020-07-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001081
更新日期：2002-01-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2010.54
更新日期：2011-08-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/sj.mp.4001809
更新日期：2006-04-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000563
更新日期：2000-01-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/sj.mp.4000232
更新日期：1997-01-01 00:00:00
abstract：:Chronic stress contributes to the development of psychiatric disorders including anxiety and depression. Several inflammatory-related effects of stress are associated with increased interleukin-1 (IL-1) signaling within the central nervous system and are mediated by IL-1 receptor 1 (IL-1R1) on several distinct cell ty...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-020-0788-3
更新日期：2020-05-22 00:00:00
