The Role of eIF5A1 in LPS-Induced Neuronal Remodeling of the Nucleus Accumbens in the Depression

作者全名:"Lyu, Qiang; Zou, Hecun; Luo, Li; Liu, Wei; He, Xiang; Shang, Fei-Fei"

作者地址:"[Liu, Wei] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Anesthesiol, Chengdu 610072, Sichuan, Peoples R China; [He, Xiang] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Shang, Fei-Fei] Fudan Univ, Huashan Hosp, Dept Anesthesiol, Shanghai 200040, Peoples R China; [He, Xiang] Guizhou Prov Peoples Hosp, Dept Anesthesiol, Guiyang 550002, Guizhou, Peoples R China; [Shang, Fei-Fei] Yale Sch Med, Dept Neurosci, New Haven, CT 06510 USA"

通信作者:"Shang, FF (通讯作者),Yale Sch Med, Dept Neurosci, New Haven, CT 06510 USA."












关键词:depression; nucleus accumbens

摘要:"Background: The pathogenesis of depression is complex, with the brain's reward system likely to play an important role. The nucleus accumbens (NAc) is a key region in the brain that integrates reward signals. Lipopolysaccharides (LPS) can induce depressive-like behaviors and enhance neuroplasticity in NAc, but the underlying mechanism is still unknown. We previously found that eukaryotic translation initiation factor A1 (eIF5A1) acts as a ribosome-binding protein to regulate protein translation and to promote neuroplasticity.Methods: In the present study, LPS was administered intraperitoneally to rats and the expression and cellular location of eIF5A1 was then investigated by RT-PCR, Western blotting and immunofluorescence. Subsequently, a neuron-specific lentivirus was used to regulate eIF5A1 expression in vivo and in vitro. Neuroplasticity was then examined by Golgi staining and by measurement of neuronal processes. Finally, proteomic analysis was used to identify proteins regulated by eIF5A1.Results: The results showed that eIF5A1 expression was significantly increased in the NAc neurons of LPS rats. Following the knockdown of eIF5A1 in NAc neurons, the LPS-induced increases in neuronal arbors and spine density were significantly attenuated. Depression-like behaviors were also reduced. Neurite outgrowth of NAc neurons in vitro also increased or decreased in parallel with the increase or decrease in eIF5A1 expression, respectively. The proteomic results showed that eIF5A1 regulates the expression of many neuroplasticity-related proteins in neurons.Conclusions: These results confirm that eIF5A1 is involved in LPS-induced depression-like behavior by increasing neuroplasticity in the NAc. Our study also suggests the brain's reward system may play an important role in the pathogenesis of depression."

基金机构:"Science & Technology Department of Sichuan Province [2021YJ0174]; National Natural Science Foundation of China [82001269, 81860234]; Scientific and Technological Research Program of Chongqing Municipal Education Commission; [KJQN202100456]"

基金资助正文:"This work was supported by the Science & Technology Department of Sichuan Province, No. 2021YJ0174 (to QL) ; and National Natural Science Foundation of China, No. 82001269 (to FFS) ; No. 81860234 (to XH) ; and Scientific and Technological Research Program of Chongqing Municipal Education Commission, No. KJQN202100456 (to FFS) . The funding bodies played no role in the study design, in the collection, analysis and interpretation of data, in the writing of the paper, and in the decision to submit the paper for publication."