GABA-cAMP Response Element-Binding Protein Signaling Regulates Maturation and Survival of Newly Generated Neurons in the Adult Hippocampus

被引：266

作者：

Jagasia, Ravi ^{[1
]}

Steib, Kathrin ^{[1
]}

Englberger, Elisabeth ^{[1
]}

Herold, Sabine ^{[1
]}

Faus-Kessler, Theresa ^{[1
]}

Saxe, Michael ^{[2
]}

Gage, Fred H. ^{[2
]}

Song, Hongjun ^{[3
]}

Lie, D. Chichung ^{[1
]}

机构：

[1] German Res Ctr Environm Hlth, Res Grp Adult Neural Stem Cells & Neurogenesis, Inst Dev Genet, Helmholtz Zentrum Munchen, D-85764 Munich, Germany

[2] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA

[3] Johns Hopkins Univ, Sch Med, Dept Neurol, Inst Cell Engn, Baltimore, MD 21205 USA

来源：

JOURNAL OF NEUROSCIENCE | 2009年 / 29卷 / 25期

关键词：

NEWBORN NEURONS; GRANULE CELLS; MORPHOLOGICAL MATURATION; TRANSCRIPTION FACTORS; DENTATE GYRUS; CREB GENE; NEUROGENESIS; DIFFERENTIATION; EXPRESSION; DOUBLECORTIN;

D O I：

10.1523/JNEUROSCI.1054-09.2009

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Survival and integration of new neurons in the hippocampal circuit are rate-limiting steps in adult hippocampal neurogenesis. Neuronal network activity is a major regulator of these processes, yet little is known about the respective downstream signaling pathways. Here, we investigate the role of cAMP response element-binding protein (CREB) signaling in adult hippocampal neurogenesis. CREB is activated in new granule neurons during a distinct developmental period. Loss of CREB function in a cell-autonomous manner impairs dendritic development, decreases the expression of the neurogenic transcription factor NeuroD and of the neuronal microtubule-associated protein, doublecortin (DCX), and compromises the survival of newborn neurons. In addition, GABA-mediated excitation regulates CREB activation at early developmental stages. Importantly, developmental defects after loss of GABA-mediated excitation can be compensated by enhanced CREB signaling. These results indicate that CREB signaling is a central pathway in adult hippocampal neurogenesis, regulating the development and survival of new hippocampal neurons downstream of GABA-mediated excitation.

引用

页码：7966 / 7977

页数：12

共 66 条

[61] Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus [J].