Lithium promotes recovery of neurological function after spinal cord injury by inducing autophagy
Lithium promotes autophagy and has a neuroprotective effect on spinal cord injury (SCI); however, the underlying mechanisms remain unclear. Therefore, in this study, we investigated the effects of lithium and the autophagy inhibitor 3-methyladenine (3-MA) in a rat model of SCI. The rats were randoml...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2018-01-01
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| Series: | Neural Regeneration Research |
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| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2018;volume=13;issue=12;spage=2191;epage=2199;aulast=Zhang |
| _version_ | 1818760493110657024 |
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| author | Duo Zhang Fang Wang Xu Zhai Xiao-Hui Li Xi-Jing He |
| author_facet | Duo Zhang Fang Wang Xu Zhai Xiao-Hui Li Xi-Jing He |
| author_sort | Duo Zhang |
| collection | DOAJ |
| description | Lithium promotes autophagy and has a neuroprotective effect on spinal cord injury (SCI); however, the underlying mechanisms remain unclear. Therefore, in this study, we investigated the effects of lithium and the autophagy inhibitor 3-methyladenine (3-MA) in a rat model of SCI. The rats were randomly assigned to the SCI, lithium, 3-MA and sham groups. In the 3-MA group, rats were intraperitoneally injected with 3-MA (3 mg/kg) 2 hours before SCI. In the lithium and 3-MA groups, rats were intraperitoneally injected with lithium (LiCl; 30 mg/kg) 6 hours after SCI and thereafter once daily until sacrifice. At 2, 3 and 4 weeks after SCI, neurological function and diffusion tensor imaging indicators were remarkably improved in the lithium group compared with the SCI and 3-MA groups. The Basso, Beattie and Bresnahan locomotor rating scale score and fractional anisotropy values were increased, and the apparent diffusion coefficient value was decreased. Immunohistochemical staining showed that immunoreactivities for Beclin-1 and light-chain 3B peaked 1 day after SCI in the lithium and SCI groups. Immunoreactivities for Beclin-1 and light-chain 3B were weaker in the 3-MA group than in the SCI group, indicating that 3-MA inhibits lithium-induced autophagy. Furthermore, NeuN+ neurons were more numerous in the lithium group than in the SCI and 3-MA groups, with the fewest in the latter. Our findings show that lithium reduces neuronal damage after acute SCI and promotes neurological recovery by inducing autophagy. The neuroprotective mechanism of action may not be entirely dependent on the enhancement of autophagy, and furthermore, 3-MA might not completely inhibit all autophagy pathways. |
| first_indexed | 2024-12-18T06:59:29Z |
| format | Article |
| id | doaj.art-976f9b0a6bee4d058bcb67dd03514725 |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-12-18T06:59:29Z |
| publishDate | 2018-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-976f9b0a6bee4d058bcb67dd035147252022-12-21T21:17:05ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742018-01-0113122191219910.4103/1673-5374.241473Lithium promotes recovery of neurological function after spinal cord injury by inducing autophagyDuo ZhangFang WangXu ZhaiXiao-Hui LiXi-Jing HeLithium promotes autophagy and has a neuroprotective effect on spinal cord injury (SCI); however, the underlying mechanisms remain unclear. Therefore, in this study, we investigated the effects of lithium and the autophagy inhibitor 3-methyladenine (3-MA) in a rat model of SCI. The rats were randomly assigned to the SCI, lithium, 3-MA and sham groups. In the 3-MA group, rats were intraperitoneally injected with 3-MA (3 mg/kg) 2 hours before SCI. In the lithium and 3-MA groups, rats were intraperitoneally injected with lithium (LiCl; 30 mg/kg) 6 hours after SCI and thereafter once daily until sacrifice. At 2, 3 and 4 weeks after SCI, neurological function and diffusion tensor imaging indicators were remarkably improved in the lithium group compared with the SCI and 3-MA groups. The Basso, Beattie and Bresnahan locomotor rating scale score and fractional anisotropy values were increased, and the apparent diffusion coefficient value was decreased. Immunohistochemical staining showed that immunoreactivities for Beclin-1 and light-chain 3B peaked 1 day after SCI in the lithium and SCI groups. Immunoreactivities for Beclin-1 and light-chain 3B were weaker in the 3-MA group than in the SCI group, indicating that 3-MA inhibits lithium-induced autophagy. Furthermore, NeuN+ neurons were more numerous in the lithium group than in the SCI and 3-MA groups, with the fewest in the latter. Our findings show that lithium reduces neuronal damage after acute SCI and promotes neurological recovery by inducing autophagy. The neuroprotective mechanism of action may not be entirely dependent on the enhancement of autophagy, and furthermore, 3-MA might not completely inhibit all autophagy pathways.http://www.nrronline.org/article.asp?issn=1673-5374;year=2018;volume=13;issue=12;spage=2191;epage=2199;aulast=Zhangnerve regeneration; spinal cord injury; lithium; secondary injury; autophagydiffusion tensor imaging; neuroprotection; functional recovery; immunohistochemistry; Beclin-1; light-chain 3B; neural regeneration |
| spellingShingle | Duo Zhang Fang Wang Xu Zhai Xiao-Hui Li Xi-Jing He Lithium promotes recovery of neurological function after spinal cord injury by inducing autophagy Neural Regeneration Research nerve regeneration; spinal cord injury; lithium; secondary injury; autophagy diffusion tensor imaging; neuroprotection; functional recovery; immunohistochemistry; Beclin-1; light-chain 3B; neural regeneration |
| title | Lithium promotes recovery of neurological function after spinal cord injury by inducing autophagy |
| title_full | Lithium promotes recovery of neurological function after spinal cord injury by inducing autophagy |
| title_fullStr | Lithium promotes recovery of neurological function after spinal cord injury by inducing autophagy |
| title_full_unstemmed | Lithium promotes recovery of neurological function after spinal cord injury by inducing autophagy |
| title_short | Lithium promotes recovery of neurological function after spinal cord injury by inducing autophagy |
| title_sort | lithium promotes recovery of neurological function after spinal cord injury by inducing autophagy |
| topic | nerve regeneration; spinal cord injury; lithium; secondary injury; autophagy diffusion tensor imaging; neuroprotection; functional recovery; immunohistochemistry; Beclin-1; light-chain 3B; neural regeneration |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2018;volume=13;issue=12;spage=2191;epage=2199;aulast=Zhang |
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