突触重建是慢性脑低灌注（Chronic Brain Hypoperfusion, CBH）认知损伤后神经功能修复的关键点。最新研究证实，糖酵解可通过影响细胞整体代谢影响突触重建，但其在CBH中的作用尚不清楚。我们前期研究发现CBH可引发神经突触丢失，并能抑制糖酵解激活；而过表达CBH时下调的端粒酶逆转录酶（TERT）可缓解神经突起退化，且可激活原本在神经元中沉默的糖酵解关键酶。故此，我们推测激活TERT可激活神经元糖酵解，延缓CBH突触退化。本课题拟在此基础上，通过明确TERT对糖酵解的激活作用，探究TERT在维持神经突触形成和认知保护中的必要性，揭示TERT驱动的代谢重组促突触重建缓解CBH脑损伤的机制，以期通过调控TERT，来维持神经元糖酵解、抵抗CBH认知损伤时的神经突触退化。本项目将为深入认识糖酵解影响突触重建的机制、探索TERT的非端粒保护作用、寻找有效的抗CBH靶点提供新思路。

Synaptic reconstruction is the key node for the long-term repair of neural function after cognitive impairment of the central nervous system. The latest studies demonstrated that glycolysis can affect the synaptic reconstruction through regulating the overall metabolism of cells, indicating that glycolysis may be related with neurocognitive injury. However, so far, the role and mechanism of glycolysis in neurocognitive injury induced by Chronic Brain Hypoperfusion (CBH) are not clear. Our previous studies found that CBH may cause the degeneration of synapses, and significantly inhibit the activation of glycolysis. Further study found that CBH can inhibit the expression of telomerase reverse transcriptase (TERT), and the overexpression of TERT can significantly improve the learning and memory ability in rats with CBH, meanwhile, though Transcriptome Array, we found that the overexpression of TERT can significantly activate the expression of PFKFB3 (fructose – 2, 6 - phosphatase - 3) which is the key enzyme of glycolysis and originally is silence in neurons. Therefore, we speculate that activation of TERT can activate glycolysis in neurons, and then delay synaptic degeneration induced by CBH. On this basis, the project intends to demonstrate the activation of glycolysis promoted by TERT, explore the necessary role of TERT in maintaining synapse formation and cognition protection, reveal the effect and mechanism of neuronal metabolism reprogramming driven by TERT promoting the synaptic reconstruction to alleviate cognitive impairment induced by CBH, in order to maintain neuronal glycolysis and counteract synaptic degeneration in CBH cognitive impairment process through regulating TERT. Our study will provide new insights for further understanding the mechanism of neuronal metabolism in regulating synaptic reconstruction, exploring the non-telomere protective role of TERT, and searching effective target of cognitive damage induced by CBH.