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Reduction of depression-like behavior in rat model induced by ShRNA targeting norepinephrine transporter in locus coeruleus
Du, Xiangdong1; Yin, Ming1; Yuan, Lian1; Zhang, Guangya1; Fan, Yan1; Li, Zhe1; Yuan, Nian1; Lv, Xiaoli1; Zhao, Xueli1; Zou, Siyun1; Deng, Wei2; Kosten, Thomas R.3; Zhang, Xiang Yang4,5
First AuthorDu, Xiangdong
Correspondent Emailxiangdong du (xiangdong-du@163.com) ; xiang yang zhang (zhangxy@psych.ac.cn)
2020-05-04
Source PublicationTRANSLATIONAL PSYCHIATRY
ISSN2158-3188
Subtypearticle
Volume10Issue:1Pages:11
Contribution Rank4
Abstract

Depression may be associated with reduced monoamine neurotransmission, particularly serotonin and norepinephrine (NE). Reuptake of NE by the norepinephrine transporter (NET) is the primary mechanism by which many of the antidepressants are high-affinity substrates for NET. This study aimed to examine the effect of lentivirus-mediated shRNA targeting NET in locus coeruleus (LC) on depression-like behaviors of rats. We randomly assigned 60 male Wistar rats to 6 experimental groups: (1) Control group: without chronic unpredictable mild stress (CUMS) and without NET-shRNA treatment; (2) shRNA group: without CUMS + NET-shRNA; (3) CUMS group: 3-week CUMS without NET-shRNA; (4) CUMS + nonsense shRNA group; (5) CUMS + amygdala (Amy)-shRNA group; (6) CUMS+ locus coeruleus (LC)-shRNA group. First, recombinant lentiviral vector expressing shRNA (ShRNA-629, ShRNA-330, ShRNA-1222, ShRNA-1146 or ShRNA- negative control) against NET were produced, and their efficiency in knocking down of NET in PC12 cells were assessed by Q-PCR and western blot analysis. Second, shRNA was injected into the rat LC bilaterally to investigate whether it could prevent the depressive-like behavior induced by 3-week CUMS. Third, we tested the depressive-like behavior of the rats in the forced swimming test, the open field test, the sucrose preference test, as well as the body weight gain at the end of the seventh week. Finally, the protein expressions of NET was measured by western blot and the NE levels were measured by high performance liquid chromatography. Q-PCR and western blot showed that the ShRNA-1146 had the best interference efficiency targeting on NET in PC12 cells (p < 0.01). Compared to the depression model group, the immobility time in the forced swimming test was significantly reduced (p < 0.01), but the sucrose preference and the total scores in the open field test were significantly increased (all p < 0.01) in the group treated with shRNA in LC. Furthermore, compared with the depression model group, NET levels were significantly decreased (p < 0.01), but NE levels were significantly increased in the group treated with shRNA in LC (p < 0.05). Our findings suggest that Lentivirus-mediated shRNA targeting NET in LC downregulated NET both in vitro and in vivo, resulting in a significant decrease in depressive-like behavior of rats.

DOI10.1038/s41398-020-0808-8
Indexed BySCI
Language英语
Funding OrganizationNational Key R&D Program of China ; Natural Science Fund Project of Jiangsu Province ; Suzhou Key Medical Center for Psychiatric Diseases ; Suzhou Clinical Medical Expert Team Introduced Project
Funding ProjectNational Key R&D Program of China[2017YFE0103700] ; Natural Science Fund Project of Jiangsu Province[BK20151197] ; Suzhou Key Medical Center for Psychiatric Diseases[Szzx201509] ; Suzhou Clinical Medical Expert Team Introduced Project[SZYJTD201715]
WOS Research AreaPsychiatry
WOS SubjectPsychiatry
WOS IDWOS:000533424100005
PublisherNATURE PUBLISHING GROUP
WOS KeywordGENE-THERAPY ; ANTIDEPRESSANT TREATMENTS ; TRANSGENE EXPRESSION ; DOPAMINE TRANSPORTER ; LENTIVIRAL VECTORS ; MAJOR DEPRESSION ; KNOCKOUT MICE ; MILD STRESS ; OPEN-LABEL ; ASSOCIATION
Citation statistics
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/31829
Collection中国科学院心理健康重点实验室
Corresponding AuthorDu, Xiangdong; Zhang, Xiang Yang
Affiliation1.Soochow Univ, Suzhou Psychiat Hosp, Affiliated Guangji Hosp, Suzhou, Peoples R China
2.Sichuan Univ, West China Hosp, Dept Psychiat & Psychiat Lab, State Key Lab Biotherapy, Chengdu, Peoples R China
3.Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA
4.Chinese Acad Sci, Inst Psychol, CAS Key Lab Mental Hlth, Beijing, Peoples R China
5.Univ Chinese Acad Sci, Dept Psychol, Beijing, Peoples R China
Corresponding Author AffilicationKey Laboratory of Mental Health, CAS
Recommended Citation
GB/T 7714
Du, Xiangdong,Yin, Ming,Yuan, Lian,et al. Reduction of depression-like behavior in rat model induced by ShRNA targeting norepinephrine transporter in locus coeruleus[J]. TRANSLATIONAL PSYCHIATRY,2020,10(1):11.
APA Du, Xiangdong.,Yin, Ming.,Yuan, Lian.,Zhang, Guangya.,Fan, Yan.,...&Zhang, Xiang Yang.(2020).Reduction of depression-like behavior in rat model induced by ShRNA targeting norepinephrine transporter in locus coeruleus.TRANSLATIONAL PSYCHIATRY,10(1),11.
MLA Du, Xiangdong,et al."Reduction of depression-like behavior in rat model induced by ShRNA targeting norepinephrine transporter in locus coeruleus".TRANSLATIONAL PSYCHIATRY 10.1(2020):11.
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