Impaired macroautophagy in oligodendrocyte precursor cells suppresses neuronal plasticity via a senescence-associated signaling.

Hong Chen, Yan-Yun Sun, Qi-Fa Li, Yu-Tong Du, Na-Na Hu, Ao-Ran Sui, Xiao-Qing Luo, Xin Huang, Chao Zhu, Gang Yang, Lin-Lin Yao, Yong Tang, Hua Hu, Chun-Feng Liu, Jin Tao, Lei Feng, Frank Kirchhoff, Wenhui Huang, Shao Li, Quan-Hong Ma

Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China. · pubmed

Paper

Abstract

Aging drives cognitive decline in the adult brain with unclear mechanisms. Previously, oligodendrocyte precursor cells (OPCs), the source cells of myelin-forming cells in the central nervous system, have been linked to brain aging by their compromised differentiation and regeneration capability. Whether a myelination-independent function of OPCs is involved in brain aging remains unknown. In this study, we herein report a myelination-independent role of OPCs in exaggerating cognitive decline in the aging brain via suppressing neuronal plasticity. Our results demonstrate that macroautophagic flux declines in aged OPCs. Inactivation of autophagy promotes the senescence of OPCs, which activates C-C motif chemokine ligand 3 (CCL3)/CCL5-C-C motif chemokine receptor 5 signaling. Through this, autophagy-defective OPCs impair glutamatergic transmission, neuronal excitability, and long-term potentiation, exaggerating the cognitive decline in the aging brain. Our study demonstrates a myelination-independent role of OPCs in brain aging and identifies that a declined autophagy in OPCs is a pivotal factor in driving aging-associated cognitive decline.

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Research summary

The paper claims that impaired macroautophagy in oligodendrocyte precursor cells exacerbates cognitive decline in the aging brain through a senescence-associated signaling pathway. This research is relevant as it explores a potential root cause of cognitive decline associated with aging, focusing on the role of oligodendrocyte precursor cells and their functions beyond myelination, which could lead to new insights in longevity and age-related cognitive decline.

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