Bexarotene promotes microglia/macrophages - Specific brain - Derived Neurotrophic factor expression and axon sprouting after traumatic brain injury
| Autor: | Yike Huang, Zhaosi Zhang, Xiaochuan Sun, Zhijian Huang, Zongduo Guo, Liu Liu, Li Jiang, Shaoqiu Jiang, Chongjie Cheng, Jianjun Zhong, Jingchuan Wu, Han Liu, Junchi He, Chao Zhou |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Gene Expression Antineoplastic Agents 03 medical and health sciences Mice 0302 clinical medicine Developmental Neuroscience Neurotrophic factors Internal medicine Brain Injuries Traumatic medicine Animals Axon Gap-43 protein Maze Learning Bexarotene Brain-derived neurotrophic factor biology Microglia business.industry Brain-Derived Neurotrophic Factor Macrophages Axons Myelin basic protein Nerve Regeneration Mice Inbred C57BL 030104 developmental biology Endocrinology medicine.anatomical_structure nervous system Neurology biology.protein Cytokine secretion business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Experimental neurology. 334 |
| ISSN: | 1090-2430 |
| Popis: | Traumatic brain injury (TBI) has been regarded as one of the leading cause of injury-related death and disability. White matter injury after TBI is characterized by axon damage and demyelination, resulting in neural network impairment and neurological deficit. Brain-derived neurotrophic factor (BDNF) can promote white matter repair. The activation of peroxisome proliferator-activated receptor gamma (PPARγ) has been reported to promote microglia/macrophages towards anti-inflammatory state and therefore to promote axon regeneration. Bexarotene, an agonist of retinoid X receptor (RXR), can activate RXR/PPARγ heterodimers. The aim of the present study was to identify the effect of bexarotene on BDNF in microglia/macrophages and axon sprouting after TBI in mice. Bexarotene was administered intraperitoneally in C57BL/6 mice undergoing controlled cortical impact (CCI). PPARγ dependency was determined by intraperitoneal administration of a PPARγ antagonist T0070907. We found that bexarotene promoted axon regeneration indicated by increased growth associated protein 43 (GAP43) expression, myelin basic protein (MBP) expression, and biotinylated dextran amine (BDA)+ axon sprouting. Bexarotene also increased microglia/macrophages-specific brain derived neurotrophic factor (BDNF) expression after TBI. In addition, bexarotene reduced the number of pro-inflammatory microglia/macrophages while increased the number of anti-inflammatory microglia/macrophages after TBI. Moreover, bexaortene inhibited pro-inflammatory cytokine secretion. In addition, bexarotene treatment improved neurological scores and cognitive function of CCI-injured mice. These effects of bexarotene were partially abolished by T0070907. In conclusion, bexarotene promotes axon sprouting, increases microglia/macrophages-specific BDNF expression, and induces microglia/macrophages from a pro-inflammatory state towards an anti-inflammatory one after TBI at least partially in a PPARγ-dependent manner. |
| Databáze: | OpenAIRE |
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