title: Changes of TSPO-mediated mitophagy signaling pathway in learned helplessness mice.
abstract: Low response rate was witnessed with the present monoaminergic based antidepressants, urging a need for new therapeutic target identification. Accumulated evidences strongly suggest that mitochondrial deficit is implicated in major depression and 18kDa translocator protein (TSPO) plays an important role in regulating mitochondrial function. However the changes of TSPO and TSPO mediated mitophagy pathway in the depressive brain is unclear. In present study, a well validated animal model of depression, learned helplessness (LH), was employed to investigate the relevant changes. Significant behavioral changes were observed in the LH mice. Results showed that TSPO and other mitophagy related proteins, such as VDAC1, Pink1 and Beclin1 were significantly decreased by LH challenge. Moreover, KIFC2, relevant to the mitochondrial transport and Snap25, relevant to neurotransmitter vesicle release, were also obviously down-regulated in the LH mice, which further rendered supportive evidence for the existing mitochondrial dysfunction in LH mice. Present results demonstrated that LH induced depressive symptoms and affected TSPO-mediated mitophagy pathway, indicating a potential target candidate for depression treatment.
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. Electronic address: liuyanyong@126.com.
authors.forename: Yanyong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. Electronic address: yangnanbeijing@126.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Zuo
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy; D003865:Major Depressive Disorder / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D015870:Gene Expression / Q000235:genetics*; D006380:Helplessness, Learned; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D063306:Mitophagy / Q000235:genetics*; D018079:Receptors, GABA / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D050995:Voltage-Dependent Anion Channel 1; D050994:Voltage-Dependent Anion Channels / Q000235:genetics
chemical_list: D000928:Antidepressive Agents; C463819:Bzrp protein, mouse; D018079:Receptors, GABA; C494762:VDAC1 protein, human; D050994:Voltage-Dependent Anion Channels; D050995:Voltage-Dependent Anion Channel 1
keywords: 18kDa translocator protein; Depression; Learned helplessness; Mitochondrial autophagy; Voltage-dependent anion channel