Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer's Disease

被引:177
作者
Sun, Binggui [1 ,2 ]
Halabisky, Brian [1 ,2 ]
Zhou, Yungui [1 ]
Palop, Jorge J. [1 ,2 ]
Yu, Guiqiu [1 ]
Mucke, Lennart [1 ,2 ]
Gan, Li [1 ,2 ]
机构
[1] Univ Calif San Francisco, Gladstone Inst Neurol Dis, San Francisco, CA 94158 USA
[2] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA
关键词
NEWLY GENERATED NEURONS; ENHANCED SYNAPTIC PLASTICITY; HIPPOCAMPAL NEUROGENESIS; AMYLOID-BETA; TRANSGENIC MICE; DENTATE GYRUS; MOUSE MODEL; MEMORY; BRAIN; INTEGRATION;
D O I
10.1016/j.stem.2009.10.003
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Adult neurogenesis regulates plasticity and function in the hippocampus, which is critical for memory and vulnerable to Alzheimer's disease (AD). Promoting neurogenesis may improve hippocampal function in AD brains. However, how amyloid 0 (AD), the key AD pathogen, affects the development and function of adult-born neurons remains unknown. Adult-born granule cells (GCs) in human amyloid precursor protein (hAPP) transgenic mice, an AD model, showed greater dendritic length, spine density, and functional responses than did controls early in development, but were impaired morphologically and functionally during later maturation. Early inhibition of GABA(A) receptors to suppress GABAergic signaling or late inhibition of calcineurin to enhance glutamatergic signaling normalized the development of adult-born GCs in hAPP mice with high A beta levels. A beta-induced increases in GABAergic neurotransmission or an imbalance between GABAergic and glutamatergic neurotransmission may contribute to impaired neurogenesis in AD.
引用
收藏
页码:624 / 633
页数:10
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