• Obayed Raihan, Afrina Brishti, Md Rasel Molla, Wenbo Li, Qilun Zhang, Peng Xu, Muhammad Imran Khan, Juan Zhang, and Qiang Liu.
• The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, School of Life Sciences, University of Science and Technology of China, Hefei 230001, China; Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, China; Neurodegenerative Disease Research Center, University of Science and Technology of China, Hefei 230026, China; CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei 230026, China.
• Neuroscience. 2018 Oct 15; 390: 160-173.

AbstractMiR-335-3p, a neuron-enriched microRNA, has been reported to be involved in aging and age-related neurological diseases. However, the role of miR-335-3p in cholesterol metabolism of astrocytes, and whether it affects neuronal functions, particularly during aging process, largely remains unknown. In this study, we uncover that miR-335-3p is significantly increased in aged cultured astrocytes and aged hippocampal brains, accompanied by decreased cellular cholesterol and diminished expression of HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) and 3-hydroxy-3-methylglutaryl-CoA synthase-1 (HMGCS1), both step-limiting enzymes in cholesterol synthesis pathway. We also demonstrate that miR-335-3p suppresses HMGCS1 post-transcriptionally by directly binding to its 3'UTR, and HMGCR through binding mediated by SFRS2. More importantly, aged mice with miR-335-3p deficiency in hippocampal brains exhibit improved learning and memory, accompanied by enhanced levels of postsynaptic density protein 95 (PSD95). We further reveal that the level change of PSD95 is resulted from altered cholesterol metabolism. Our findings provide a novel insight into the regulatory role of miR-335-3p in cholesterol metabolism in astrocytes, and consequently cognitive functions during aging.Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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