Neuronostatin (NST) is an endogenous peptide hormone, it has the ability to improve oligomeric Aβ (oAβ)-induced cognitive impairments and increase blood glucose levels in mice. However, the relationship between NST and oAβ regarding brain glucose metabolism has not yet been established. The present study defined the contributions of NST and oAβ in the brain glucose metabolism in mice. It was found that i.c.v. co-administration of NST (3 nmol/mouse) and oAβ (1 nmol/mouse) decreased the mRNA expressions of glucose-6-phosphate dehydrogenase and phosphofructokinase. The treatments were observed to reduce ATP production and the enzyme activities of glucose-6-phosphate dehydrogenase and hexokinase in both the cortex and hippocampus. Simultaneously, co-injection of NST and oAβ inhibited the mRNA and protein expression of glucose transporters GLUT3 and GLUT1 in the cortex and hippocampus. NST promoted the oAβ-induced decreased the cortical NeuN staining, while oAβ increased the levels of NST in both the cortex and hippocampus. I.c.v. co-administration of NST and oAβ led to increase the levels of GPR107 expression and the phosphorylation of PKA, Akt, PERK and eIF-2α in the cortex. These findings suggest that NST promoted oAβ-induced dysfunctional glucose metabolism through the GPR107/PKA/Akt signaling pathway and PERK/eIF2α axis in the brain, which thus contributes to metabolic dysfunction and Alzheimer’s disease (AD) pathophysiology.

神经抑素（NST）是一种内源性肽激素，具有改善寡聚Aβ（oAβ）诱导的认知障碍并增加小鼠血糖水平的能力。然而，关于脑葡萄糖代谢的NST和oAβ之间的关系尚未建立。本研究定义了NST和oAβ在小鼠脑葡萄糖代谢中的作用。发现icv与NST（3 nmol /小鼠）和oAβ（1 nmol /小鼠）共同给药可降低葡萄糖-6-磷酸脱氢酶和磷酸果糖激酶的mRNA表达。观察到这些处理降低了皮层和海马中的ATP产生以及葡萄糖6-磷酸脱氢酶和己糖激酶的酶活性。同时，NST和oAβ的共同注射抑制了皮质和海马中葡萄糖转运蛋白GLUT3和GLUT1的mRNA和蛋白表达。NST促进oAβ诱导的皮质NeuN染色减少，而oAβ升高皮质和海马中的NST水平。NST和oAβ的Icv共同给药导致皮质中GPR107表达水平升高以及PKA，Akt，PERK和eIF-2α磷酸化。这些发现表明，NST通过大脑中的GPR107 / PKA / Akt信号传导途径和PERK /eIF2α轴促进了oAβ诱导的功能障碍性葡萄糖代谢，从而促进了代谢功能障碍和阿尔茨海默氏病（AD）的病理生理。而oAβ增加了皮质和海马中NST的水平。NST和oAβ的Icv共同给药导致皮质中GPR107表达水平升高以及PKA，Akt，PERK和eIF-2α磷酸化。这些发现表明，NST通过大脑中的GPR107 / PKA / Akt信号传导途径和PERK /eIF2α轴促进了oAβ诱导的功能障碍性葡萄糖代谢，从而促进了代谢功能障碍和阿尔茨海默氏病（AD）的病理生理。而oAβ增加了皮质和海马中NST的水平。NST和oAβ的Icv共同给药导致皮质中GPR107表达水平升高以及PKA，Akt，PERK和eIF-2α磷酸化。这些发现表明，NST通过大脑中的GPR107 / PKA / Akt信号传导途径和PERK /eIF2α轴促进了oAβ诱导的功能障碍性葡萄糖代谢，从而促进了代谢功能障碍和阿尔茨海默氏病（AD）的病理生理。