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Based on the CREB/BDNF pathway:Investigation of the effects of the kidney-benefiting and turbidity-resolving formula on learning,memory,and neuronal synaptic plasticity in senescence accelerated mouse-prone 8
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DOI   10.11656/j.issn.1673-9043.2026.06.11
Key Words   Yishen Huazuo Formula;alzheimer’s disease;cAMP response element-binding protein;brain-derived neurotrophic factor;synaptic plasticity
Author NameAffiliationE-mail
GONG Haoran Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
ZHAO Xinwei Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
WANG Kai The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China  
NI Daoyan The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China  
CUI Mengyuan Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
LIU Zhengyuan Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
JIANG Yue The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China  
ZHANG Linlin The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China zllcr@163.com 
Abstract
    [Objective] To investigate the effects of early intervention with the Yishen Huazuo Formula on learning and memory abilities,hippocampal synaptic structure and function,and the expression of proteins related to the cAMP response element-binding protein(CREB)/brain-derived neurotrophic factor(BDNF) pathway in SAMP8 mice,a model of accelerated aging. [Methods] Twenty-four 3-month-old male SAMP8 mice were randomly divided into a model(SAMP8) group and a Yishen Huazhuo Formula(YHD) group,with 12 mice in each group. Twelve male SAMR1 mice of the same age were selected as the control(SAMR1) group. The YHD group received oral administration of Yishen Huazhuo Formula granule solution,while the other two groups received the same dose of saline solution,administered once daily for 12 weeks. After administration,learning and memory abilities were evaluated using the Morris water maze test;Long-term potentiation(LTP) tests assessed synaptic neurophysiological function;Western blot analysis detected expression levels of proteins related to the “CREB/BDNF signaling pathway” in hippocampal tissue. [Results] Compared with the SAMP8 group,the YHD group showed significantly shorter escape latency times on days 4 and 5(P<0.05,P<0.01),with a trend toward increased platform crossings;The magnitude of LTP-induced fEPSP amplitude and slope enhancement was markedly elevated(P<0.05). Following TBS stimulation,the slope enhancement of LTP-induced fEPSP showed a significant increase(P<0.05). CREB protein expression was significantly increased(P<0.01),while BDNF and MecP2 protein expression showed an upward trend. p250GAP protein expression exhibited a downward trend without significant differences. [Conclusion] Early intervention with Yishen Huazuo Formula effectively improves learning and memory functions in SAMP8 mice. This may be related to its regulation of protein expression in the “CREB/BDNF signaling pathway,” improvement of neuronal ultrastructure,and subsequent enhancement of neuronal synaptic function.

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