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Abstract
Nuclear distribution element-like 1 (NDEL1) enzyme activity is important for neuritogenesis, neuronal migration, and neurodevelopment. We reported previously lower NDEL1 enzyme activity in blood of treated first episode psychosis and chronic schizophrenia (SCZ) compared to healthy control subjects, with even lower activity in treatment resistant chronic SCZ patients, implicating NDEL1 activity in SCZ. Herein, higher NDEL1 activity was observed in the blood and several brain regions of a validated animal model for SCZ at baseline. In addition, long-term treatment with typical or atypical antipsychotics, under conditions in which SCZ-like phenotypes were reported to be reversed in this animal model for SCZ, showed a significant NDEL1 activity reduction in blood and brain regions which is in line with clinical data. Importantly, these results support measuring NDEL1 enzyme activity in the peripheral blood to predict changes in NDEL1 activity in the CNS. Also, acute administration of psychostimulants, at levels reported to induce SCZ-like phenotype in normal rat strains, increased NDEL1 enzyme activity in blood. Therefore, alterations in NDEL1 activity after treatment with antipsychotics or psychostimulants may suggest a possible modulation of NDEL1 activity secondary to neurotransmission homeostasis and provide new insights into the role of NDEL1 in SCZ pathophysiology.
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1 Universidade Federal de São Paulo (UNIFESP), Departamento de Farmacologia, Escola Paulista de Medicina (EPM), São Paulo, Brazil (GRID:grid.411249.b) (ISNI:0000 0001 0514 7202); Universidade Federal de São Paulo (UNIFESP), Department of Psychiatry, Escola Paulista de Medicina (EPM), São Paulo, Brazil (GRID:grid.411249.b) (ISNI:0000 0001 0514 7202); National Institute for Translational Medicine (INCT-TM, CNPq/FAPESP/CAPES), Ribeirão Preto, Brazil (GRID:grid.411249.b)
2 Johns Hopkins University, Department of Psychiatry and Behavioral Sciences, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311)
3 Universidade Federal de São Paulo (UNIFESP), Departamento de Farmacologia, Escola Paulista de Medicina (EPM), São Paulo, Brazil (GRID:grid.411249.b) (ISNI:0000 0001 0514 7202); National Institute for Translational Medicine (INCT-TM, CNPq/FAPESP/CAPES), Ribeirão Preto, Brazil (GRID:grid.411249.b)
4 Instituto Butantan, Laboratory of Immunochemistry, São Paulo, Brazil (GRID:grid.418514.d) (ISNI:0000 0001 1702 8585)
5 Universidade Federal de São Paulo (UNIFESP), Department of Biophysics, Escola Paulista de Medicina (EPM), São Paulo, Brazil (GRID:grid.411249.b) (ISNI:0000 0001 0514 7202)
6 Universidade Federal de São Paulo (UNIFESP), Department of Psychiatry, Escola Paulista de Medicina (EPM), São Paulo, Brazil (GRID:grid.411249.b) (ISNI:0000 0001 0514 7202)