Polysaccharides from Ganoderma lucidum Promote Cognitive Function and Neural Progenitor Proliferation in Mouse Model of Alzheimer's Disease

Shichao Huang; Jianxin Mao; Kan Ding; Yue Zhou; Xianglu Zeng; Wenjuan Yang; Peipei Wang; Cun Zhao; Jian Yao; Peng Xia; Gang Pei

doi:10.1016/j.stemcr.2016.12.007

Polysaccharides from Ganoderma lucidum Promote Cognitive Function and Neural Progenitor Proliferation in Mouse Model of Alzheimer's Disease

Stem Cell Reports. 2017 Jan 10;8(1):84-94. doi: 10.1016/j.stemcr.2016.12.007.

Authors

Shichao Huang¹, Jianxin Mao², Kan Ding³, Yue Zhou⁴, Xianglu Zeng⁵, Wenjuan Yang⁶, Peipei Wang⁷, Cun Zhao⁶, Jian Yao⁷, Peng Xia⁸, Gang Pei⁹

Affiliations

¹ Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-based Bio-medicine, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
² State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; Graduate School, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
³ Glycochemistry & Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
⁴ State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
⁵ Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-based Bio-medicine, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; School of Life Science and Technology, the Collaborative Innovation Center for Brain Science, Tongji University, Shanghai 200092, China.
⁶ State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; Graduate School, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China.
⁷ Graduate School, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; Glycochemistry & Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
⁸ Shanghai Green Valley Pharmaceutical Co., Ltd, Shanghai 201200, China.
⁹ Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-based Bio-medicine, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; School of Life Science and Technology, the Collaborative Innovation Center for Brain Science, Tongji University, Shanghai 200092, China. Electronic address: [email protected].

Abstract

Promoting neurogenesis is a promising strategy for the treatment of cognition impairment associated with Alzheimer's disease (AD). Ganoderma lucidum is a revered medicinal mushroom for health-promoting benefits in the Orient. Here, we found that oral administration of the polysaccharides and water extract from G. lucidum promoted neural progenitor cell (NPC) proliferation to enhance neurogenesis and alleviated cognitive deficits in transgenic AD mice. G. lucidum polysaccharides (GLP) also promoted self-renewal of NPC in cell culture. Further mechanistic study revealed that GLP potentiated activation of fibroblast growth factor receptor 1 (FGFR1) and downstream extracellular signal-regulated kinase (ERK) and AKT cascades. Consistently, inhibition of FGFR1 effectively blocked the GLP-promoted NPC proliferation and activation of the downstream cascades. Our findings suggest that GLP could serve as a regenerative therapeutic agent for the treatment of cognitive decline associated with neurodegenerative diseases.

Keywords: Alzheimer's disease; Ganoderma lucidum; adult neurogenesis; cognition; fibroblast growth factor receptor 1.

MeSH terms

Alzheimer Disease / drug therapy
Alzheimer Disease / metabolism*
Alzheimer Disease / psychology*
Animals
Cell Proliferation / drug effects
Cell Self Renewal / drug effects
Cognition / drug effects*
Disease Models, Animal
Fungal Polysaccharides / pharmacology*
Mice
Mice, Transgenic
Neural Stem Cells / drug effects*
Neural Stem Cells / metabolism*
Neurogenesis / drug effects
Receptor, Fibroblast Growth Factor, Type 1 / genetics
Receptor, Fibroblast Growth Factor, Type 1 / metabolism
Reishi / chemistry*
Signal Transduction / drug effects

Substances

Fungal Polysaccharides
Receptor, Fibroblast Growth Factor, Type 1