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(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

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Nani, V, Joao ; Fonseca, Matheus C. [1] ; Engi, Sheila A. [2] ; Perillo, Mayara G. [2] ; Dias, Carlos S. B. [3] ; Gazarini, Marcos L. [4] ; Korth, Carsten [5] ; Cruz, Fabio C. [2] ; Hayashi, Mirian A. F. [2, 5]
Total Authors: 9
[1] CNPEM, Lab Nacl Biociencias LNBio, Campinas - Brazil
[2] Nani, Joao, V, Univ Fed Sao Paulo UNIFESP, Dept Farmacol, Sao Paulo - Brazil
[3] CNPEM, LNLS, Campinas - Brazil
[4] Univ Fed Sao Paulo UNIFESP, Dept Biociencias, Santos, SP - Brazil
[5] Heinrich Heine Univ Dusseldorf, Dept Neuropathol, Dusseldorf - Germany
Total Affiliations: 5
Document type: Journal article
Web of Science Citations: 0

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)

FAPESP's process: 14/50891-1 - INCT 2014: Translational Medicine
Grantee:Jaime Eduardo Cecilio Hallak
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 18/20014-0 - The gut-brain connection: role of the gut microbioma in the outcome and development of the sporadic Parkinson's disease
Grantee:Matheus de Castro Fonseca
Support Opportunities: Regular Research Grants
FAPESP's process: 17/02413-1 - Validation of crotamine as a biomarker and evaluation of its potential use in the therapy of human diseases
Grantee:Mirian Akemi Furuie Hayashi
Support Opportunities: Regular Research Grants
FAPESP's process: 19/09207-3 - Study of molecular and cellular mechanisms in mental disorders
Grantee:João Victor Silva Nani
Support Opportunities: Scholarships in Brazil - Doctorate