| Full text | |
| Author(s): |
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
|
| Affiliation: | [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 |
| Source: | JOURNAL OF PSYCHOPHARMACOLOGY; v. 34, n. 4 JAN 2020. |
| Web of Science Citations: | 0 |
| Abstract | |
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 |