(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)
Decreased nuclear distribution nudE-like 1 enzyme activity in an animal model with dysfunctional disrupted-in-schizophrenia 1 signaling featuring aberrant neurodevelopment and amphetamine-supersensitivity
Nani, V, Joao
Fonseca, Matheus C.
Engi, Sheila A.
Perillo, Mayara G.
Dias, Carlos S. B.
Gazarini, Marcos L.
Cruz, Fabio C.
Hayashi, Mirian A. F.
Total Authors: 9
 CNPEM, Lab Nacl Biociencias LNBio, Campinas - Brazil
 Nani, Joao, V, Univ Fed Sao Paulo UNIFESP, Dept Farmacol, Sao Paulo - Brazil
 CNPEM, LNLS, Campinas - Brazil
 Univ Fed Sao Paulo UNIFESP, Dept Biociencias, Santos, SP - Brazil
 Heinrich Heine Univ Dusseldorf, Dept Neuropathol, Dusseldorf - Germany
Total Affiliations: 5
JOURNAL OF PSYCHOPHARMACOLOGY;
Web of Science Citations:
Background: Interaction of nuclear-distribution element-like 1 with disrupted-in-schizophrenia 1 protein is crucial for neurite outgrowth/neuronal migration, and this interaction competitively inhibits nuclear-distribution element-like 1 peptidase activity. Nuclear-distribution element-like 1 activity is reduced in antipsychotic-naive first-episode psychosis and in medicated chronic schizophrenia, with even lower activity in treatment-resistant schizophrenia. Aims: The purpose of this study was to investigate in a rat model overexpressing human non-mutant disrupted-in-schizophrenia 1, with consequent dysfunctional disrupted-in-schizophrenia 1 signaling, the relation of nuclear-distribution element-like 1 activity with neurodevelopment and dopamine-related phenotypes. Methods: We measured cell distribution in striatum and cortex by histology and microtomography, and quantified the basal and amphetamine-stimulated locomotion and nuclear-distribution element-like 1 activity (in blood and brain) of transgenic disrupted-in-schizophrenia 1 rat vs wild-type littermate controls. Results: 3D assessment of neuronal cell body number and spatial organization of mercury-impregnated neurons showed defective neuronal positioning, characteristic of impaired cell migration, in striatum/nucleus accumbens, and prefrontal cortex of transgenic disrupted-in-schizophrenia 1 compared to wild-type brains. Basal nuclear-distribution element-like 1 activity was lower in the blood and also in several brain regions of transgenic disrupted-in-schizophrenia 1 compared to wild-type. Locomotion and nuclear-distribution element-like 1 activity were both significantly increased by amphetamine in transgenic disrupted-in-schizophrenia 1, but not in wild-type. Conclusions: Our findings in the transgenic disrupted-in-schizophrenia 1 rat allow us to state that decreased nuclear-distribution element-like 1 activity reflects both a trait (neurodevelopmental phenotype) and a state (amphetamine-induced dopamine release). We thus define here a role for decreased nuclear-distribution element-like 1 peptidase activity both for the developing brain (the neurodevelopmental phenotype) and for the adult (interaction with dopaminergic responses), and present nuclear-distribution element-like 1 activity in a novel way, as unifying neurodevelopmental with dysfunctional dopamine response phenotypes. (AU)