Lentiviral-Mediated Overexpression of the 18 kDa Translocator Protein (TSPO) in the Hippocampal Dentate Gyrus Ameliorates LPS-Induced Cognitive Impairment in Mice
Wei Wang, Liming Zhang, Xiaoying Zhang, Rui Xue, Lei Li, Weixing Zhao, Qiang Fu, Weidong Mi, Yunfeng Li
Abstract
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 test and the Morris water maze 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.
Pharmacology, Toxicology and Pharmaceutical Science
3
11%
Biochemistry, Genetics and Molecular Biology
1
4%
Psychology
1
4%
Other
3
11%
Unknown
8
30%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 November 2016.
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#3,211,141
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Outputs from Frontiers in Pharmacology
#1,406
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#57,440
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Outputs of similar age from Frontiers in Pharmacology
#22
of 160 outputs
Altmetric has tracked 22,893,031 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 16,195 research outputs from this source. They receive a mean Attention Score of 4.9. This one has done particularly well, scoring higher than 90% of its peers.
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We're also able to compare this research output to 160 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 85% of its contemporaries.
