Regrowing the adult brain: NF-κB controls functional circuit formation and tissue homeostasis in the dentate gyrus.
Regrowing the adult brain: NF-κB controls functional circuit formation and tissue homeostasis in the dentate gyrus.
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DOI：
10.1371/journal.pone.0030838
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kaltschmidt B
中科院分区：
文献类型：
--
作者：
Imielski Y;Schwamborn JC;Lüningschrör P;Heimann P;Holzberg M;Werner H;Leske O;Püschel AW;Memet S;Heumann R;Israel A;Kaltschmidt C;Kaltschmidt B
衰老过程中的认知能力下降与大脑内细胞的持续丧失有关，尤其是海马体内的细胞，这些细胞可以通过成人神经发生再生。在这里，我们表明，NF-κB的基因消融导致海马神经源性区域（齿状回）的严重缺陷。尽管干细胞增殖增加，轴突生成，突触和神经保护受到阻碍，导致苔藓纤维通路的中断和老化过程中的齿状回萎缩。在这里，NF-κB控制FOXO 1和PKA的转录，调节轴突发生。结构缺陷最终导致模式分离的行为障碍。NF-κB的重新激活导致新生神经元的整合，最终导致齿状回的再生，伴随着结构和行为缺陷的完全恢复。这些数据表明NF-κB是齿状回组织稳态的重要调节因子，提示NF-κB是治疗认知和情绪障碍的治疗靶点。
Cognitive decline during aging is correlated with a continuous loss of cells within the brain and especially within the hippocampus, which could be regenerated by adult neurogenesis. Here we show that genetic ablation of NF-κB resulted in severe defects in the neurogenic region (dentate gyrus) of the hippocampus. Despite increased stem cell proliferation, axogenesis, synaptogenesis and neuroprotection were hampered, leading to disruption of the mossy fiber pathway and to atrophy of the dentate gyrus during aging. Here, NF-κB controls the transcription of FOXO1 and PKA, regulating axogenesis. Structural defects culminated in behavioral impairments in pattern separation. Re-activation of NF-κB resulted in integration of newborn neurons, finally to regeneration of the dentate gyrus, accompanied by a complete recovery of structural and behavioral defects. These data identify NF-κB as a crucial regulator of dentate gyrus tissue homeostasis suggesting NF-κB to be a therapeutic target for treating cognitive and mood disorders.
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影响因子：
56.9
作者：
Brun, VH;Otnæss, MK;Moser, EI
通讯作者：
Moser, EI
DOI：
10.1523/jneurosci.2456-10.2011
发表时间：
2011-04-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Boersma MC;Dresselhaus EC;De Biase LM;Mihalas AB;Bergles DE;Meffert MK
通讯作者：
Meffert MK
DOI：
10.1037/h0077579
发表时间：
1979-01-01
期刊：
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
BARNES, CA
通讯作者：
BARNES, CA
影响因子：
7.2
作者：
Kaltschmidt, Barbara;Kaltschmidt, Christian
通讯作者：
Kaltschmidt, Christian
影响因子：
4.6
作者：
Gavalda, Nuria;Gutierrez, Humberto;Davies, Alun M.
通讯作者：
Davies, Alun M.