The beneficial effect of synbiotics consumption on Alzheimer's disease mouse model via reducing local and systemic inflammation.

Alzheimer's disease (AD) is a neurodegenerative disease that impairs multiple memory domains without an effective prevention or treatment approach. Amyloid plaque-induced neuroinflammation exacerbates neurodegeneration and cognitive impairment in AD. To reduce neuroinflammation, we applied prebiotics or synbiotics to modulate the gut-brain axis in the AD mouse model. AD-like deficits were reduced in mice treated with synbiotics, suggesting that dietary modulation of the gut-brain axis is a potential approach to delay AD progression.

Follistatin mediates learning and synaptic plasticity via regulation of Asic4 expression in the hippocampus.

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 overexpression 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.