Over-expression of TSPO in the hippocampal CA1 area alleviates cognitive dysfunction caused by lipopolysaccharide in mice.
The translocator protein 18kDa (TSPO) is closely related to regulation of immune/inflammatory response. However, the putative role and signaling mechanisms of TSPO in regulation of neuroinflammation remain unclear. GV287 lentiviral vectors mediating TSPO over-expression were injected into bilateral hippocampal CA1 areas to test whether TSPO over-expression was neuroprotective in lipopolysaccharide (LPS)-induced mice model. Finasteride, a blocker of allopregnanolone production, was used to test whether the protective effects were related to steroideogenesis. The results demonstrated that TSPO over-expression increased progesterone and allopregnanolone synthesis. TSPO over-expression in CA1 area improved LPS-induced cognitive deficiency in mice and this cognitive improvement was reversed by finasteride administration. These data suggest that up-regulation of TSPO level during neuroinflammation may be an adaptive response mechanism, a way to provide more neurosteroids. We confer that TSPO could be an attractive drug target for controlling neuroinflammation in the future.
Department of Neurosurgery, Air Force General Hospital of the Chinese PLA, Beijing 100142, China; Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
Hui
H
Zhang
Department of Anesthesiology, Chinese PLA Army General hospital, Beijing 100700, China.
Li
L
Ma
Department of Anesthesiology, Chinese PLA Army General hospital, Beijing 100700, China.
Yan-Ling
YL
Yin
Department of Neurosurgery, Air Force General Hospital of the Chinese PLA, Beijing 100142, China.
Lian-Qiang
LQ
Dong
Department of Neurosurgery, Air Force General Hospital of the Chinese PLA, Beijing 100142, China.
Gang-Ge
GG
Cheng
Department of Anesthesiology, Chinese PLA Army General hospital, Beijing 100700, China. Electronic address: ma_yq126@126.com.
Ya-Qun
YQ
Ma
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China. Electronic address: lyf619@aliyun.com.
Yun-Feng
YF
Li
Department of Neurosurgery, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China. Electronic address: bn_xu@yahoo.com.
Bai-Nan
BN
Xu
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000150:complications / Q000378:metabolism*; D004660:Encephalitis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D018120:Finasteride / Q000008:administration & dosage; D005822:Genetic Vectors / Q000008:administration & dosage; D016086:Lentivirus / Q000502:physiology; D008070:Lipopolysaccharides; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011280:Pregnanolone / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
C463819:Bzrp protein, mouse; D008070:Lipopolysaccharides; D018079:Receptors, GABA; D011374:Progesterone; D018120:Finasteride; D011280:Pregnanolone
Allopregnanolone; Cognition; Finasteride; Lps; Neuroinflammation; Tspo