Kim Sun Yong, Yoon Kyeong-No, Ji Jungeun, Kim Min-Gyun, Choi Seung Ah, Park Gunhyuk, Lee Won-Woo, Chung Jin Ho, Kim Sang Jeong, An Joon-Yong, Lee Dong Hun, Lee Yong-Seok
Department of Physiology, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
Mol Brain. 2025 Aug 16;18(1):69. doi: 10.1186/s13041-025-01242-6.
Substance P (SP) is a neuropeptide that functions in both the central and peripheral nervous systems. Although the peripheral actions of SP in regulating inflammatory responses have been extensively investigated, the effects of elevated peripheral SP on hippocampal functions such as spatial learning and memory remains unclear, even though SP can cross the blood-brain barrier. In this study, we found that male mice subcutaneously injected with SP for 14 days exhibited significant deficits in hippocampus-dependent memory, as assessed by the object place recognition and novel object recognition tests. In addition, long-term potentiation (LTP) at the hippocampal CA3-CA1 synapse was reduced in SP-treated mice. Transcriptomic analyses identified 77 differentially expressed genes (DEGs), and enrichment analysis highlighted pathways related to synaptic transmission, learning, and memory. These results suggest a novel skin-brain neuropeptide signaling axis. Targeting peripheral SP or its receptor may provide a therapeutic avenue for cognitive dysfunction associated with peripheral inflammation.
P物质（SP）是一种在中枢和外周神经系统中均发挥作用的神经肽。尽管SP在调节炎症反应中的外周作用已得到广泛研究，但外周SP水平升高对海马功能（如空间学习和记忆）的影响仍不清楚，尽管SP能够穿过血脑屏障。在本研究中，我们发现皮下注射SP 14天的雄性小鼠在依赖海马体的记忆方面表现出显著缺陷，这通过物体位置识别和新物体识别测试进行评估。此外，经SP处理的小鼠海马CA3-CA1突触处的长时程增强（LTP）降低。转录组分析鉴定出77个差异表达基因（DEG），富集分析突出了与突触传递、学习和记忆相关的通路。这些结果提示了一种新的皮肤-脑神经肽信号轴。靶向外周SP或其受体可能为与外周炎症相关的认知功能障碍提供一种治疗途径。
