期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2109040118
关键词
adult neurogenesis; learning; follistatin; hippocampus; Asic4
资金
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01HD032067]
- Chang Gung Memorial Hospital [CMRPD1H0413]
- Healthy Aging Research Center [EMRPD1I0501]
- Ministry of Science and Technology of Taiwan [MOST 105-2320-B-182-040]
- Molecular Medicine Research Center, Chang Gung University from The Featured Areas Research Center Program by the Ministry of Education in Taiwan [EMRPD1L0341]
- [AS-CFII-108-106]
The study identifies follistatin (Fst) as a key player in learning and adult neurogenesis, with Fst knockout leading to deficits in spatial learning and memory. Overexpression of Fst can reverse these impairments, suggesting a critical role for Fst in cognitive functions.
The biological mechanisms underpinning learning are unclear. Mounting evidence has suggested that adult hippocampal neurogenesis is involved although a causal relationship has not been well defined. Here, using high-resolution genetic mapping of adult neurogenesis, combined with sequencing information, we identify follistatin (Fst) and demonstrate its involvement in learning and adult neurogenesis. We confirmed that brain-specific Fst knockout (KO) mice exhibited decreased hippocampal neurogenesis and demonstrated that FST is critical for learning. Fst KO mice exhibit deficits in spatial learning, working memory, and long-term potentiation (LTP). In contrast, hippocampal overexpression of Fst in KO mice reversed these impairments. By utilizing RNA sequencing and chromatin immunoprecipitation, we identified Asic4 as a target gene regulated by FST and show that Asic4 plays a critical role in learning deficits caused by Fst deletion. Long-term over expression of hippocampal Fst in C57BL/6 wild-type mice alleviates age related decline in cognition, neurogenesis, and LTP. Collectively, our study reveals the functions for FST in adult neurogenesis and learning behaviors.
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