Effects of CXCR7-neutralizing antibody on neurogenesis in the hippocampal dentate gyrus and cognitive function in the chronic phase of cerebral ischemia
Stromal cell-derived factor-1 and its receptor CXCR4 are essential regulators of the neurogenesis that occurs in the adult hippocampal dentate gyrus. However, the effects of CXCR7, a new atypical receptor of stromal cell-derived factor-1, on hippocampal neurogenesis after a stroke remain largely unk...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2020-01-01
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| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=6;spage=1079;epage=1085;aulast=Dong |
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| author | Bing-Chao Dong Mei-Xuan Li Xiao-Yin Wang Xi Cheng Yu Wang Ting Xiao Jukka Jolkkonen Chuan-Sheng Zhao Shan-Shan Zhao |
| author_facet | Bing-Chao Dong Mei-Xuan Li Xiao-Yin Wang Xi Cheng Yu Wang Ting Xiao Jukka Jolkkonen Chuan-Sheng Zhao Shan-Shan Zhao |
| author_sort | Bing-Chao Dong |
| collection | DOAJ |
| description | Stromal cell-derived factor-1 and its receptor CXCR4 are essential regulators of the neurogenesis that occurs in the adult hippocampal dentate gyrus. However, the effects of CXCR7, a new atypical receptor of stromal cell-derived factor-1, on hippocampal neurogenesis after a stroke remain largely unknown. Our study is the first to investigate the effect of a CXCR7-neutralizing antibody on neurogenesis in the dentate gyrus and the associated recovery of cognitive function of rats in the chronic stage of cerebral ischemia. The rats were randomly divided into sham, sham + anti-CXCR7, ischemia and ischemia + anti-CXCR7 groups. Endothelin-1 was injected in the ipsilateral motor cortex and striatum to induce focal cerebral ischemia. Sham group rats were injected with saline instead of endothelin-1 via intracranial injection. Both sham and ischemic rats were treated with intraventricular infusions of CXCR7-neutralizing antibodies for 6 days 1 week after surgery. Immunofluorescence staining with doublecortin, a marker for neuronal precursors, was performed to assess the neurogenesis in the dentate gyrus. We found that anti-CXCR7 antibody infusion enhanced the proliferation and dendritic development of doublecortin-labeled cells in the dentate gyrus in both ischemic and sham-operated rats. Spatial learning and memory functions were assessed by Morris water maze tests 30–32 days after ischemia. CXCR7-neutralizing antibody treatment significantly reduced the escape latency of the spatial navigation trial and increased the time spent in the target quadrant of spatial probe trial in animals that received ischemic insult, but not in sham operated rats. These results suggest that CXCR7-neutralizing antibody enhances the neurogenesis in the dentate gyrus and improves the cognitive function after cerebral ischemia in rats. All animal experimental protocols and procedures were approved by the Institutional Animal Care and Use Committee of China Medical University (CMU16089R) on December 8, 2016. |
| first_indexed | 2024-12-22T20:09:33Z |
| format | Article |
| id | doaj.art-3ef957d624f646ed807487c2245d61a8 |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-12-22T20:09:33Z |
| publishDate | 2020-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-3ef957d624f646ed807487c2245d61a82022-12-21T18:14:04ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742020-01-011561079108510.4103/1673-5374.270416Effects of CXCR7-neutralizing antibody on neurogenesis in the hippocampal dentate gyrus and cognitive function in the chronic phase of cerebral ischemiaBing-Chao DongMei-Xuan LiXiao-Yin WangXi ChengYu WangTing XiaoJukka JolkkonenChuan-Sheng ZhaoShan-Shan ZhaoStromal cell-derived factor-1 and its receptor CXCR4 are essential regulators of the neurogenesis that occurs in the adult hippocampal dentate gyrus. However, the effects of CXCR7, a new atypical receptor of stromal cell-derived factor-1, on hippocampal neurogenesis after a stroke remain largely unknown. Our study is the first to investigate the effect of a CXCR7-neutralizing antibody on neurogenesis in the dentate gyrus and the associated recovery of cognitive function of rats in the chronic stage of cerebral ischemia. The rats were randomly divided into sham, sham + anti-CXCR7, ischemia and ischemia + anti-CXCR7 groups. Endothelin-1 was injected in the ipsilateral motor cortex and striatum to induce focal cerebral ischemia. Sham group rats were injected with saline instead of endothelin-1 via intracranial injection. Both sham and ischemic rats were treated with intraventricular infusions of CXCR7-neutralizing antibodies for 6 days 1 week after surgery. Immunofluorescence staining with doublecortin, a marker for neuronal precursors, was performed to assess the neurogenesis in the dentate gyrus. We found that anti-CXCR7 antibody infusion enhanced the proliferation and dendritic development of doublecortin-labeled cells in the dentate gyrus in both ischemic and sham-operated rats. Spatial learning and memory functions were assessed by Morris water maze tests 30–32 days after ischemia. CXCR7-neutralizing antibody treatment significantly reduced the escape latency of the spatial navigation trial and increased the time spent in the target quadrant of spatial probe trial in animals that received ischemic insult, but not in sham operated rats. These results suggest that CXCR7-neutralizing antibody enhances the neurogenesis in the dentate gyrus and improves the cognitive function after cerebral ischemia in rats. All animal experimental protocols and procedures were approved by the Institutional Animal Care and Use Committee of China Medical University (CMU16089R) on December 8, 2016.http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=6;spage=1079;epage=1085;aulast=Dongcerebral ischemia; cognitive function; cxcr7; dendritic development; dentate gyrus; doublecortin; neurogenesis; neutralizing antibody; stroke; stromal cell-derived factor-1 |
| spellingShingle | Bing-Chao Dong Mei-Xuan Li Xiao-Yin Wang Xi Cheng Yu Wang Ting Xiao Jukka Jolkkonen Chuan-Sheng Zhao Shan-Shan Zhao Effects of CXCR7-neutralizing antibody on neurogenesis in the hippocampal dentate gyrus and cognitive function in the chronic phase of cerebral ischemia Neural Regeneration Research cerebral ischemia; cognitive function; cxcr7; dendritic development; dentate gyrus; doublecortin; neurogenesis; neutralizing antibody; stroke; stromal cell-derived factor-1 |
| title | Effects of CXCR7-neutralizing antibody on neurogenesis in the hippocampal dentate gyrus and cognitive function in the chronic phase of cerebral ischemia |
| title_full | Effects of CXCR7-neutralizing antibody on neurogenesis in the hippocampal dentate gyrus and cognitive function in the chronic phase of cerebral ischemia |
| title_fullStr | Effects of CXCR7-neutralizing antibody on neurogenesis in the hippocampal dentate gyrus and cognitive function in the chronic phase of cerebral ischemia |
| title_full_unstemmed | Effects of CXCR7-neutralizing antibody on neurogenesis in the hippocampal dentate gyrus and cognitive function in the chronic phase of cerebral ischemia |
| title_short | Effects of CXCR7-neutralizing antibody on neurogenesis in the hippocampal dentate gyrus and cognitive function in the chronic phase of cerebral ischemia |
| title_sort | effects of cxcr7 neutralizing antibody on neurogenesis in the hippocampal dentate gyrus and cognitive function in the chronic phase of cerebral ischemia |
| topic | cerebral ischemia; cognitive function; cxcr7; dendritic development; dentate gyrus; doublecortin; neurogenesis; neutralizing antibody; stroke; stromal cell-derived factor-1 |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=6;spage=1079;epage=1085;aulast=Dong |
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