| http://purl.uniprot.org/citations/32610340 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32610340 | http://www.w3.org/2000/01/rdf-schema#comment | "Schizophrenia is a debilitating disorder affecting young adults displaying symptoms of cognitive impairment, anxiety, and early social isolation prior to episodes of auditory hallucinations. Cannabis use has been tied to schizophrenia-like symptoms, indicating that dysregulated endogenous cannabinoid signaling may be causally linked to schizophrenia. Previously, we reported that glutamatergic neuron-selective ablation of Lmo4, an endogenous inhibitor of the tyrosine phosphatase PTP1B, impairs endocannabinoid (eCB) production from the metabotropic glutamate receptor mGluR5. These Lmo4-deficient mice display anxiety-like behaviors that are alleviated by local shRNA knockdown or pharmacological inhibition of PTP1B that restores mGluR5-dependent eCB production in the amygdala. Here, we report that these Lmo4-deficient mice also display schizophrenia-like behaviors: impaired working memory assessed in the Y maze and defective sensory gating by prepulse inhibition of the acoustic startle response. Modulation of inhibitory inputs onto layer 2/3 pyramidal neurons of the prefrontal cortex relies on eCB signaling from the brain-derived neurotrophic factor receptor trkB, rather than mGluR5, and this mechanism was defective in Lmo4-deficient mice. Genetic ablation of PTP1B in the glutamatergic neurons lacking Lmo4 restored tyrosine phosphorylation of trkB, trkB-mediated eCB signaling, and ameliorated schizophrenia-like behaviors. Pharmacological inhibition of PTP1B with trodusquemine also restored trkB phosphorylation and improved schizophrenia-like behaviors by restoring eCB signaling, since the CB1 receptor antagonist 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide blocked this effect. Thus, activation of PTP1B in pyramidal neurons contributes to schizophrenia-like behaviors in Lmo4-deficient mice and genetic or pharmacological intervention targeting PTP1B ameliorates schizophrenia-related deficits."xsd:string |
| http://purl.uniprot.org/citations/32610340 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41386-020-0755-3"xsd:string |
| http://purl.uniprot.org/citations/32610340 | http://purl.uniprot.org/core/author | "Zhang L."xsd:string |
| http://purl.uniprot.org/citations/32610340 | http://purl.uniprot.org/core/author | "Qin Z."xsd:string |
| http://purl.uniprot.org/citations/32610340 | http://purl.uniprot.org/core/author | "Chen H.H."xsd:string |
| http://purl.uniprot.org/citations/32610340 | http://purl.uniprot.org/core/author | "Stewart A.F.R."xsd:string |
| http://purl.uniprot.org/citations/32610340 | http://purl.uniprot.org/core/author | "Cruz S.A."xsd:string |
| http://purl.uniprot.org/citations/32610340 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32610340 | http://purl.uniprot.org/core/name | "Neuropsychopharmacology"xsd:string |
| http://purl.uniprot.org/citations/32610340 | http://purl.uniprot.org/core/pages | "1884-1895"xsd:string |
| http://purl.uniprot.org/citations/32610340 | http://purl.uniprot.org/core/title | "Activation of tyrosine phosphatase PTP1B in pyramidal neurons impairs endocannabinoid signaling by tyrosine receptor kinase trkB and causes schizophrenia-like behaviors in mice."xsd:string |
| http://purl.uniprot.org/citations/32610340 | http://purl.uniprot.org/core/volume | "45"xsd:string |
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