ProBDNF Signaling Regulates Depression-Like Behaviors in Rodents under Chronic Stress
| Autor: | Yin-Yin Bai, Ting-Hua Wang, Chun-Sheng Ruan, Yue-Qing Zeng, Xin-Fu Zhou, Li Zhou, Jia-yi Li, Hong Liao, Larisa Bobrovskaya, Chang-Fu Tian, Zhi-Long Kang, Dennis Liu, Chun-Rui Yang |
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| Přispěvatelé: | Bai, Yin-Yin, Ruan, Chun-Sheng, Yang, Chun-Rui, Li, Jia-Yi, Kang, Zhi-Long, Zhou, Li, Liu, Dennis, Zeng, Yue-Qing, Wang, Ting-Hua, Tian, Chang-Fu, Liao, Hong, Bobrovskaya, Larisa, Zhou, Xin-Fu |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Hippocampus Tropomyosin receptor kinase B Mice 0302 clinical medicine anti-proBDNF antibodies Chronic stress brain-derived neurotropic factor Neocortex Brain Psychiatry and Mental health medicine.anatomical_structure depression Antidepressive Agents Second-Generation Original Article Psychology chronically stressed rats medicine.drug Signal Transduction medicine.medical_specialty Dendritic Spines Antibodies 03 medical and health sciences Food Preferences Downregulation and upregulation Internal medicine Fluoxetine medicine Animals Protein Precursors Rats Wistar Swimming Pharmacology Depressive Disorder Brain-Derived Neurotrophic Factor medicine.disease Rats Mice Inbred C57BL Disease Models Animal 030104 developmental biology Mood Endocrinology Mood disorders Gene Expression Regulation Chronic Disease Exploratory Behavior mood regulation Neuroscience 030217 neurology & neurosurgery Stress Psychological |
| Popis: | Chronic exposure to stressful environment is a key risk factor contributing to the development of depression. However, the mechanisms involved in this process are still unclear. Brain-derived neurotropic factor (BDNF) has long been investigated for its positive role in regulation of mood, although the role of its precursor, proBDNF, in regulation of mood is not known. In this study, using an unpredictable chronic mild stress (UCMS) paradigm we found that the protein levels of proBDNF were increased in the neocortex and hippocampus of stressed mice and this UCMS-induced upregulation of proBDNF was abolished by chronic administration of fluoxetine. We then established a rat model of UCMS and found that the expression of proBDNF/p75NTR/sortilin was upregulated, whereas the expression of mature BDNF and TrkB was downregulated in both neocortex and hippocampus of chronically stressed rats. Finally, we found that the injection of anti-proBDNF antibody via intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) approaches into the UCMS rats significantly reversed the stress-induced depression-like behavior and restored the exploratory activity and spine growth. Although intramuscular injection of AAV-proBDNF did not exacerbate the UCMS-elicited rat mood-related behavioral or pathological abnormalities, i.c.v. injection of AAV-proBDNF increased the depression-like behavior in naive rats. Our findings suggest that proBDNF plays a role in the development of chronic stress-induced mood disturbances in rodents. Central (i.c.v.) or peripheral (i.p.) inhibition of proBDNF by injecting specific anti-proBDNF antibodies may provide a novel therapeutic approach for the treatment of stress-related mood disorders. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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