Presenilin-1 Dependent Neurogenesis Regulates Hippocampal Learning and Memory

被引:33
作者
Bonds, Jacqueline A. [1 ,2 ]
Kuttner-Hirshler, Yafit [2 ]
Bartolotti, Nancy [2 ]
Tobin, Matthew K. [1 ,2 ,3 ]
Pizzi, Michael [4 ]
Marr, Robert [5 ]
Lazarov, Orly [1 ,2 ]
机构
[1] Univ Illinois, Grad Program Neurosci, Chicago, IL 60612 USA
[2] Univ Illinois, Coll Med, Dept Anat & Cell Biol, Chicago, IL 60612 USA
[3] Univ Illinois, Med Scientist Training Program, Chicago, IL 60612 USA
[4] Midwestern Univ, Downers Grove, IL 60515 USA
[5] Rosalind Franklin Univ Med & Sci, Dept Neurosci, N Chicago, IL 60064 USA
基金
美国国家卫生研究院;
关键词
GAMMA-SECRETASE ACTIVITY; NEURAL STEM-CELLS; ADULT NEUROGENESIS; ALZHEIMERS-DISEASE; BETA-CATENIN; NATIONAL INSTITUTE; ASSOCIATION; CLEAVAGE; ENDOPROTEOLYSIS; DIFFERENTIATION;
D O I
10.1371/journal.pone.0131266
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Presenilin-1 (PS1), the catalytic core of the aspartyl protease gamma-secretase, regulates adult neurogenesis. However, it is not clear whether the role of neurogenesis in hippocampal learning and memory is PS1-dependent, or whether PS1 loss of function in adult hippocampal neurogenesis can cause learning and memory deficits. Here we show that downregulation of PS1 in hippocampal neural progenitor cells causes progressive deficits in pattern separation and novelty exploration. New granule neurons expressing reduced PS1 levels exhibit decreased dendritic branching and dendritic spines. Further, they exhibit reduced survival. Lastly, we show that PS1 effect on neurogenesis is mediated via beta-catenin phosphorylation and notch signaling. Together, these observations suggest that impairments in adult neurogenesis induce learning and memory deficits and may play a role in the cognitive deficits observed in Alzheimer's disease.
引用
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页数:22
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