PTPRR regulates ERK dephosphorylation in depression mice model

Abstract

BackgroundThe 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. MethodsLentiviral 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. ResultsWithout 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. ConclusionThe 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.