(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)
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.
Número total de Autores: 9
Afiliação do(s) autor(es):
 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
Número total de Afiliações: 5
Tipo de documento:
JOURNAL OF PSYCHOPHARMACOLOGY;
Citações Web of Science:
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)