title: PTPRR regulates ERK dephosphorylation in depression mice model.
abstract: BACKGROUND
  The Protein tyrosine phosphatase receptor type R (PTPRR), which regulates the dephosphorylation of the downstream mitogen-activated protein kinase (MAPK) steering cell proliferation, apoptosis and synaptic plasticity, may be involved in the pathogenesis of depression.
  
  
  METHODS
  Lentiviral vectors were utilized to express the PTPRR constitutively in the hippocampal dentate gyrus (DG) of mice before or after chronic mild stress. Behavior tests, MAPK levels, neuronal apoptosis and cell proliferation in the hippocampal DG were examined.
  
  
  RESULTS
  Without chronic mild stress (CMS), the lenti-shPTPRR mice showed shorter immobility time in the tail suspension test than controls, while the lenti-PTPRR mice exhibited significantly less sucrose intake and increased immobility time in the forced swim tests than control mice, indicating increased prodepressant-like effects of PTPRR in lenti-PTPRR mice. Similarly, under CMS, the lenti-shPTPRR mice had more sucrose intake, shorter immobility time in the forced swim test and tail suspension test compared to controls, and lenti-PTPRR mice had less sucrose intake and longer immobility time in forced swim test and tail suspension test, exhibiting increased susceptibility to depressive-like behaviors and greater sensitivity to CMS. Besides, the Phospho-ERK1/2(p-ERK) had significant lower phosphorylation in lenti-PTPRR group and higher expression in lenti-shPTPRR group, both without CMS. The Lenti-PTPRR mice exposed to CMS had significant lower p-ERK, and the lenti-shPTPRR mice exposed to CMS had significant higher p-ERK and lower p-P38. Moreover, there were more cells underwent apoptosis in lenti-PTPRR group ,with and without CMS. In cell proliferation, less BrdU positive cells were observed in lenti-PTPRR mice than controls.
  
  
  CONCLUSIONS
  The site-speciﬁc lentiviral injections resulted in the PTPRR over-expression in the hippocampal DG and subsequent increased ERK dephosphorylation, which leads to more neuron apoptosis, less cell proliferation, depression onset and increased sensitivity to CMS. PTPRR/ERK pathway could be potential target for depression therapy.
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Zhifen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Animal center of Tsinghua university, Beijing, China.
authors.forename: Zhongchen
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China. Electronic address: krzhang_sxmu@vip.163.com.
authors.forename: Kerang
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000378:metabolism; D003863:Depression / Q000378:metabolism*; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D010766:Phosphorylation; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7 / Q000378:metabolism*; D013550:Swimming
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; C513472:Ptprr protein, mouse; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7
keywords: Chronic mild stress; Depression; Extracellar signal-regulated kinase; Mitogen-activated protein kinase; Protein tyrosine phosphatase receptor type R