The deletion of dicer in mature myelinating glial cells causes progressive axonal degeneration but not overt demyelination in adult mice
| Autor: | Jingjing Wang, Lan Xiao, Nanxin Huang, Jianqin Niu, Xing Gao, Shouyu Wang, Yu-Jian Yang, Zhifang Li, Tao Li, Feng Mei, Fei Wang, Hongkai Wang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
Ribonuclease III 0301 basic medicine Neurofilament genetic processes Central nervous system Mice Transgenic Motor Activity DEAD-box RNA Helicases 03 medical and health sciences Cellular and Molecular Neuroscience Myelin 0302 clinical medicine Atrophy Conditional gene knockout medicine Animals Paralysis Axon Myelin Sheath biology fungi food and beverages Optic Nerve medicine.disease Sciatic Nerve White Matter Axons Cell biology Mice Inbred C57BL enzymes and coenzymes (carbohydrates) 030104 developmental biology medicine.anatomical_structure Spinal Cord nervous system Neurology Peripheral nervous system Nerve Degeneration Disease Progression biology.protein Ataxia Female 030217 neurology & neurosurgery Dicer |
| Zdroj: | Glia. 66:1960-1971 |
| ISSN: | 0894-1491 |
| DOI: | 10.1002/glia.23450 |
| Popis: | Myelinating glial cells (MGCs), oligodendrocytes (OLs) in the central nervous system (CNS) and Schwann cells (SCs) in the peripheral nervous system (PNS), generate myelin sheaths that insulate axons. After myelination is completed in adulthood, MGC functions independent from myelin are required to support axon survival, but the underlying mechanisms are still unclear. Dicer is a key enzyme that is responsible for generating functional micro-RNAs (miRNAs). Despite the importance of Dicer in initiating myelination, the role of Dicer in mature MGCs is still unclear. Here, Dicer was specifically deleted in mature MGCs in 2-month old mice (PLP-CreERT; Dicer fl/fl) by tamoxifen administration. Progressive motor dysfunction was observed in the Dicer conditional knockout mice, which displayed hind limb ataxia at 3 months post recombination that deteriorated into paralysis within 5 months. Massive axonal degeneration/atrophy in peripheral nerves was responsible for this phenomenon, but overt demyelination was not observed in either the CNS or PNS. In contrast to the PNS, signs of axonal degeneration were not observed in the CNS of these animals. We induced a Dicer deletion in oligodendroglia at postnatal day 5 in NG2-CreERT; Dicer fl/fl mice to evaluate whether Dicer expression in OLs is essential for axonal survival. Dicer deletion in oligodendroglia did not cause motor dysfunction at the age of 7 months. Neither axonal atrophy nor demyelination was observed in the CNS. Based on our results, Dicer expression in SCs is required to maintain axon integrity in adult PNS, and Dicer is dispensable for maintaining myelin sheaths in MGCs. |
| Databáze: | OpenAIRE |
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