Lentiviral-mediated overexpression of the 18 kDa translocator protein (TSPO) in the hippocampal dentate gyrus ameliorates LPS - induced cognitive impairment in mice
The 18 kDa translocator protein (TSPO) is involved in the immune/inflammatory response. However, the exact role that TSPO plays in neuroinflammation-induced cognitive impairment is still elusive. The purpose of our present study was to investigate the effects of lentiviral-mediated hippocampal overe...
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| Format: | Article |
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Frontiers Media S.A.
2016-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00384/full |
| _version_ | 1819199006314594304 |
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| author | Wei Wang Wei Wang Liming Zhang Xiaoying Zhang Rui Xue Lei Li Weixing Zhao Qiang Fu Weidong Mi Yun-Feng Li |
| author_facet | Wei Wang Wei Wang Liming Zhang Xiaoying Zhang Rui Xue Lei Li Weixing Zhao Qiang Fu Weidong Mi Yun-Feng Li |
| author_sort | Wei Wang |
| collection | DOAJ |
| description | The 18 kDa translocator protein (TSPO) is involved in the immune/inflammatory response. However, the exact role that TSPO plays in neuroinflammation-induced cognitive impairment is still elusive. The purpose of our present study was to investigate the effects of lentiviral-mediated hippocampal overexpression of the TSPO in a mouse model of LPS-induced cognitive impairment. We established a mouse cognitive impairment model using systematic daily administration of lipopolysaccharide (LPS) (0.5 mg/kg). Microinjection of the dentate gyrus of the mouse with lentiviral vectors, which contained a cDNA targeting TSPO (Lv-TSPO), resulted in a significant increase in TSPO expression and allopregnanolone production. Mice treated with LPS showed cognitive deficits in the novel object recognition (NOR) test and the Morris water maze (MWM) test that could be ameliorated by TSPO overexpression. In addition, TSPO overexpression reversed LPS-induced microglial activation and accumulation of pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α. Moreover, TSPO overexpression attenuated the LPS-induced impairment of hippocampal neurogenesis. Our results suggest that local overexpression of TSPO in the hippocampal dentate gyrus alleviated LPS-induced cognitive deficits, and its effects might be mediated by the attenuation of inflammatory cytokines, inhibition of microglial activation, and promotion of neurogenesis. |
| first_indexed | 2024-12-23T03:09:28Z |
| format | Article |
| id | doaj.art-9975579fbb3b407ba122661f2ca55a4f |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-23T03:09:28Z |
| publishDate | 2016-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-9975579fbb3b407ba122661f2ca55a4f2022-12-21T18:02:15ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122016-10-01710.3389/fphar.2016.00384216896Lentiviral-mediated overexpression of the 18 kDa translocator protein (TSPO) in the hippocampal dentate gyrus ameliorates LPS - induced cognitive impairment in miceWei Wang0Wei Wang1Liming Zhang2Xiaoying Zhang3Rui Xue4Lei Li5Weixing Zhao6Qiang Fu7Weidong Mi8Yun-Feng Li9Chinese PLA General HospitalThe General Hospital of the PLA Rocket ForceBeijing Institue of Pharmacology and ToxicologyChinese PLA General HospitalBeijing Institue of Pharmacology and ToxicologyHebei North UniversityChinese PLA General HospitalChinese PLA General HospitalChinese PLA General HospitalBeijing Institue of Pharmacology and ToxicologyThe 18 kDa translocator protein (TSPO) is involved in the immune/inflammatory response. However, the exact role that TSPO plays in neuroinflammation-induced cognitive impairment is still elusive. The purpose of our present study was to investigate the effects of lentiviral-mediated hippocampal overexpression of the TSPO in a mouse model of LPS-induced cognitive impairment. We established a mouse cognitive impairment model using systematic daily administration of lipopolysaccharide (LPS) (0.5 mg/kg). Microinjection of the dentate gyrus of the mouse with lentiviral vectors, which contained a cDNA targeting TSPO (Lv-TSPO), resulted in a significant increase in TSPO expression and allopregnanolone production. Mice treated with LPS showed cognitive deficits in the novel object recognition (NOR) test and the Morris water maze (MWM) test that could be ameliorated by TSPO overexpression. In addition, TSPO overexpression reversed LPS-induced microglial activation and accumulation of pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α. Moreover, TSPO overexpression attenuated the LPS-induced impairment of hippocampal neurogenesis. Our results suggest that local overexpression of TSPO in the hippocampal dentate gyrus alleviated LPS-induced cognitive deficits, and its effects might be mediated by the attenuation of inflammatory cytokines, inhibition of microglial activation, and promotion of neurogenesis.http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00384/fullHippocampusNeurogenesisNeuroinflammationAllopregnanoloneTSPOCognitive impairment |
| spellingShingle | Wei Wang Wei Wang Liming Zhang Xiaoying Zhang Rui Xue Lei Li Weixing Zhao Qiang Fu Weidong Mi Yun-Feng Li Lentiviral-mediated overexpression of the 18 kDa translocator protein (TSPO) in the hippocampal dentate gyrus ameliorates LPS - induced cognitive impairment in mice Frontiers in Pharmacology Hippocampus Neurogenesis Neuroinflammation Allopregnanolone TSPO Cognitive impairment |
| title | Lentiviral-mediated overexpression of the 18 kDa translocator protein (TSPO) in the hippocampal dentate gyrus ameliorates LPS - induced cognitive impairment in mice |
| title_full | Lentiviral-mediated overexpression of the 18 kDa translocator protein (TSPO) in the hippocampal dentate gyrus ameliorates LPS - induced cognitive impairment in mice |
| title_fullStr | Lentiviral-mediated overexpression of the 18 kDa translocator protein (TSPO) in the hippocampal dentate gyrus ameliorates LPS - induced cognitive impairment in mice |
| title_full_unstemmed | Lentiviral-mediated overexpression of the 18 kDa translocator protein (TSPO) in the hippocampal dentate gyrus ameliorates LPS - induced cognitive impairment in mice |
| title_short | Lentiviral-mediated overexpression of the 18 kDa translocator protein (TSPO) in the hippocampal dentate gyrus ameliorates LPS - induced cognitive impairment in mice |
| title_sort | lentiviral mediated overexpression of the 18 kda translocator protein tspo in the hippocampal dentate gyrus ameliorates lps induced cognitive impairment in mice |
| topic | Hippocampus Neurogenesis Neuroinflammation Allopregnanolone TSPO Cognitive impairment |
| url | http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00384/full |
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