Gong Han, Zhao Hang, Mao Xueying
Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
Foods. 2025 May 29;14(11):1938. doi: 10.3390/foods14111938.
As the global elderly population is rising, concerns about cognitive decline and memory loss are becoming urgent. This study evaluated the potential of sea cucumber hydrolysates (SCH) from in alleviating cognitive deficits using a D-galactose-induced murine aging model. The effects of SCH on behavior, hippocampal morphology, gut microbiota, hippocampal cholinergic system, brain-derived neurotrophic factor (BDNF) signaling, and neuroinflammatory pathways were investigated. Results showed that SCH ameliorated learning and memory deficits and reduced neuronal damage in aging mice. SCH also modulated gut microbiota, along with increased fecal short-chain fatty acids levels. Functional prediction revealed that alterations in gut microbiota were related to signal transduction. Further, SCH enhanced hippocampal cholinergic function through elevating acetylcholine (ACh) levels and inhibiting acetylcholinesterase (AChE) activity and activated BDNF signaling, consistent with predictions of gut microbiota function. Restoration of cholinergic homeostasis and transmission of the BDNF pathway might contribute to the inhibition of hippocampal neuroinflammation via suppressing microglial activation and the nuclear factor kappa-B (NF-κB) pathway. In summary, SCH attenuated cognitive deficits through suppressing neuroinflammation, which might be correlated with the signal transduction caused by regulating gut microbiota. Further validation will be conducted through microbiota depletion and fecal microbiota transplantation. These findings suggest that SCH is a promising functional component for counteracting aging-related cognitive deficits.
随着全球老年人口的增加，对认知衰退和记忆力丧失的担忧日益迫切。本研究使用D-半乳糖诱导的小鼠衰老模型评估了海参水解物（SCH）缓解认知缺陷的潜力。研究了SCH对行为、海马形态、肠道微生物群、海马胆碱能系统、脑源性神经营养因子（BDNF）信号传导和神经炎症途径的影响。结果表明，SCH改善了衰老小鼠的学习和记忆缺陷，并减少了神经元损伤。SCH还调节了肠道微生物群，同时粪便短链脂肪酸水平增加。功能预测表明，肠道微生物群的改变与信号转导有关。此外，SCH通过提高乙酰胆碱（ACh）水平和抑制乙酰胆碱酯酶（AChE）活性增强了海马胆碱能功能，并激活了BDNF信号传导，这与肠道微生物群功能的预测一致。胆碱能稳态的恢复和BDNF途径的传递可能通过抑制小胶质细胞活化和核因子κB（NF-κB）途径来抑制海马神经炎症。总之，SCH通过抑制神经炎症减轻了认知缺陷，这可能与调节肠道微生物群引起的信号转导有关。将通过微生物群耗竭和粪便微生物群移植进行进一步验证。这些发现表明，SCH是一种有前途的功能性成分，可对抗与衰老相关的认知缺陷。
