Depression-like behaviors induced by defective PTPRT activity through dysregulated synaptic functions and neurogenesis

Cited 1 time in scopus
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Title
Depression-like behaviors induced by defective PTPRT activity through dysregulated synaptic functions and neurogenesis
Author(s)
So-Hee Lim; S Shin; M H Kim; E C Kim; Da Yong LeeJeonghee Moon; Hey-Yeon Park; Young-Kyoung Ryu; Young Mi Kang; Y J Kang; Tae Hwan Kim; Na-Yoon Lee; Nam-Soon Kim; Dae Yeul Yu; I Shim; Y Gondo; M Satake; E Kim; Kyoung Shim Kim; S S Min; Jae-Ran Lee
Bibliographic Citation
Journal of Cell Science, vol. 133, pp. jcs243972-jcs243972
Publication Year
2020
Abstract
PTPRT has been known to regulate synaptic formation and dendritic arborization of hippocampal neurons. PTPRT-/- null and PTPRT-Asp401Ala mutant mice displayed enhanced depression-like behaviors compared with wild-type mice. The transient knockdown of PTPRT in dentate gyrus enhanced the depression-like behaviors of wild-type mice, while the rescued expression of PTPRT ameliorated the behaviors of PTPRT-null mice. The chronic stress exposure reduced the expression of PTPRT in the hippocampus of mice. In PTPRT-deficient mice the expressions of GluR2 were attenuated through dysregulated tyrosine phosphorylation and the long-term potentiation at perforant-dentate gyrus synapses was augmented. The inhibitory synaptic transmissions of dentate gyrus and hippocampal GABA concentration were reduced in PTPRT-deficient mice. In addition the hippocampal expression of GABA transporter GAT3 was decreased and its tyrosine phosphorylation was increased in PTPRT-deficient mice. PTPRT-deficient mice displayed reduced newborn granule cells in their dentate gyrus and the attenuated neurogenic ability of embryonic hippocampal neural stem cells. In conclusion, our findings show that the physiological roles of PTPRT on hippocampal neurogenesis as well as synaptic functions are involved in the pathogenesis of depressive disorder.
Keyword
PTPRTDepressionKnockoutTyrosine dephosphorylationSynaptic functionHippocampal neurogenesis
ISSN
0021-9533
Publisher
Company Biologists Ltd
DOI
http://dx.doi.org/10.1242/jcs.243972
Type
Article
Appears in Collections:
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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