The molecular neural mechanism underlying the acceleration of brain aging due to Dcf1 deficiency

IF 2.6 3区医学 Q3 NEUROSCIENCES

Molecular and Cellular Neuroscience Pub Date : 2023-09-01 DOI:10.1016/j.mcn.2023.103884

Haicong Zhou , Jiao Wang , Tieqiao Wen

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Abstract

Owing to the continuous increase in human life expectancy, the management of aging-related diseases has become an urgent issue. The brain dominates the central nervous system; therefore, brain aging is a key area of aging-related research. We previously uncovered that dendritic cell factor 1 (Dcf1) maintains the stemness of neural stem cells and its expression in Drosophila can prolong lifespan, suggesting an association between Dcf1 and aging; however, the specific underlying neural mechanism remains unclear. In the present study, we show for the first time that hippocampal neurogenesis is decreased in aged Dcf1^−/− mice, which leads to a decrease in the number of brain neurons and an increased number of senescent cells. Moreover, astrocytes proliferate abnormally and express elevated mRNA levels of aging-related factors, in addition to displaying increased activation of Akt and Foxo3a. Finally, behavioral tests confirm that aged Dcf1^−/− mice exhibit a significant decline in cognitive abilities related to learning and memory. In conclusion, we reveal a novel mechanism underlying brain aging triggered by Dcf1 deficiency at the molecular, cellular, tissue, and behavioral levels, providing a new perspective for the exploration of brain aging.

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Dcf1缺乏导致脑老化加速的分子神经机制

随着人类预期寿命的不断延长，老龄化相关疾病的管理已成为一个紧迫的问题。大脑支配着中枢神经系统；因此，大脑衰老是衰老相关研究的一个关键领域。我们之前发现，树突状细胞因子1（Dcf1）维持神经干细胞的干性，其在果蝇中的表达可以延长寿命，这表明Dcf1与衰老之间存在联系；然而，具体的潜在神经机制尚不清楚。在本研究中，我们首次表明，衰老的Dcf1−/−小鼠的海马神经发生减少，这导致大脑神经元数量减少，衰老细胞数量增加。此外，星形胶质细胞异常增殖，表达衰老相关因子的mRNA水平升高，此外表现出Akt和Foxo3a的激活增加。最后，行为测试证实，衰老的Dcf1−/−小鼠表现出与学习和记忆相关的认知能力显著下降。总之，我们在分子、细胞、组织和行为层面揭示了Dcf1缺乏引发大脑衰老的新机制，为探索大脑衰老提供了新的视角。

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来源期刊

Molecular and Cellular Neuroscience 医学-神经科学

CiteScore

5.60

自引率

0.00%

发文量

审稿时长

37 days

期刊介绍： Molecular and Cellular Neuroscience publishes original research of high significance covering all aspects of neurosciences indicated by the broadest interpretation of the journal''s title. In particular, the journal focuses on synaptic maintenance, de- and re-organization, neuron-glia communication, and de-/regenerative neurobiology. In addition, studies using animal models of disease with translational prospects and experimental approaches with backward validation of disease signatures from human patients are welcome.