Type 1 diabetes (T1D) has been reported to cause cognitive decline, but brain metabolic changes during this process are still far from being fully understood. Here, we found that streptozotocin (STZ)-induced T1D mice exhibited impaired learning and memory at 11 weeks after STZ treatment but not at 3 weeks. Therefore, we studied metabolic alterations in six different brain regions of T1D mice with and without cognitive decline, and attempted to identify key metabolic pathways related to diabetic cognitive dysfunction. The results demonstrate that lactate had already increased in all brain regions of T1D mice prior to cognitive decline, but a decreased TCA cycle was only observed in hippocampus, cortex and striatum of T1D mice with cognitive impairment. Reduced N-acetylaspartate and choline were found in all brain regions of T1D mice, irrespective of cognitive decline. In addition, disrupted neurotransmitter metabolism was noted to occur in T1D mice before cognitive deficit. Of note, we found that the level of uridine was significantly reduced in cerebellum, cortex, hypothalamus and midbrain of T1D mice when cognitive decline was presented. Therefore, brain region-specific metabolic alterations may comprise possible biomarkers for the early-diagnosis and monitoring of diabetic cognitive decline. Moreover, down-regulated TCA cycle and pyrimidine metabolism could be closely related to T1D-associated cognitive impairment.

据报道，1 型糖尿病 (T1D) 会导致认知能力下降，但在此过程中大脑代谢的变化仍远未完全了解。在这里，我们发现链脲佐菌素 (STZ) 诱导的 T1D 小鼠在 STZ 治疗后 11 周时表现出学习和记忆受损，但在 3 周时没有。因此，我们研究了有和没有认知能力下降的 T1D 小鼠六个不同大脑区域的代谢改变，并试图确定与糖尿病认知功能障碍相关的关键代谢途径。结果表明，在认知能力下降之前，T1D 小鼠所有大脑区域的乳酸已经增加，但仅在认知障碍的 T1D 小鼠的海马、皮质和纹状体中观察到 TCA 循环减少。在 T1D 小鼠的所有大脑区域中都发现了减少的 N-乙酰天冬氨酸和胆碱，与认知能力下降无关。此外，在认知缺陷之前，T1D 小鼠中出现神经递质代谢紊乱。值得注意的是，我们发现当出现认知能力下降时，T1D 小鼠的小脑、皮层、下丘脑和中脑的尿苷水平显着降低。因此，大脑区域特异性代谢改变可能包含用于糖尿病认知能力下降的早期诊断和监测的可能生物标志物。此外，下调的 TCA 循环和嘧啶代谢可能与 T1D 相关的认知障碍密切相关。当出现认知能力下降时，T1D 小鼠的下丘脑和中脑。因此，大脑区域特异性代谢改变可能包含用于糖尿病认知能力下降的早期诊断和监测的可能生物标志物。此外，下调的 TCA 循环和嘧啶代谢可能与 T1D 相关的认知障碍密切相关。当出现认知能力下降时，T1D 小鼠的下丘脑和中脑。因此，大脑区域特异性代谢改变可能包含用于糖尿病认知能力下降的早期诊断和监测的可能生物标志物。此外，下调的 TCA 循环和嘧啶代谢可能与 T1D 相关的认知障碍密切相关。