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目的 明确链脲佐菌素(STZ)诱导的糖尿病小鼠内侧前额叶皮层(mPFC)全脑直接输入神经环路是否发生重塑，并结合葡萄糖代谢与行为学变化，挖掘糖尿病认知障碍(DCD)的潜在神经环路机制。方法 将雄性C57BL/6J小鼠随机分为对照组(CON)与糖尿病模型组(DM),造模后通过葡萄糖耐量实验评估糖代谢水平，采用Morris水迷宫、新物体识别实验分别检测空间学习记忆与识别记忆能力；利用狂犬病毒单突触逆向示踪技术，对小鼠mPFC全脑直接输入神经元进行标记、成像与定量分析。结果 模型组小鼠体重降低、空腹血糖升高，葡萄糖耐量受损，同时空间学习记忆与短时、长时识别记忆均出现显著减退；mPFC上游输入神经元广泛分布于皮层、丘脑等脑区，且糖尿病状态下多个脑区的输入比例发生显著改变。结论 本研究构建了STZ糖尿病小鼠mPFC全脑直接输入图谱的分析体系，结合代谢与行为学数据，为阐释糖尿病认知障碍的前额叶环路重塑机制提供了解剖学依据。
Abstract：Objective To determine whether remodeling occurs in the whole-brain direct input neural circuits to the mouse medial prefrontal cortex(mPFC) in streptozotocin(STZ)-induced diabetic mice, and to elucidate the potential neural circuit mechanisms underlying diabetic cognitive dysfunction(DCD) by integrating findings on glucose metabolism and behavioral changes.Methods Male C57BL/6J mice were randomly assigned to a control group(CON) and a diabetes model group(DM).Following model establishment, glucose metabolism was assessed via glucose tolerance tests, while spatial learning memory and recognition memory were evaluated using the Morris water maze and novel object recognition tests, respectively.Rabies virus-based monosynaptic retrograde tracing was employed to label, image, and quantitatively analyze the whole-brain direct input neurons projecting to the mPFC.Results The results showed that the model group presented decreased body weight, elevated fasting blood glucose, impaired glucose tolerance, as well as significant decline in spatial learning memory and short/long-term recognition memory.The upstream input neurons to the mPFC were widely distributed in cortex, thalamus and other brain regions, and the input proportion of multiple brain regions changed notably under diabetic condition.Conclusion This study established an analytical framework for mapping direct whole-brain inputs to the mPFC in STZ-induced diabetic mice.By integrating metabolic and behavioral data, it provides an anatomical basis for elucidating the mechanisms of prefrontal circuit remodeling underlying diabetes-associated cognitive impairment.
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基本信息:
DOI：10.16751/j.cnki.2095-4646.2026042701
中图分类号:R587.2;R749.1
引用信息:
[1]刘钰蓉,杨润鹏,刘启胜,等.糖尿病小鼠内侧前额叶皮层全脑输入环路与认知功能研究[J].湖北科技学院学报(医学版),2026,40(04):277-282+287+272.DOI:10.16751/j.cnki.2095-4646.2026042701.
基金信息:
国家自然科学基金青年项目(82301383); 湖北科技学院博士启动基金(BK202514)
2026-04-27
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