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Haloperidol Affects Plasticity of Differentiated NG-108 Cells Through σ1R/IPR1 Complex. | LitMetric

Haloperidol Affects Plasticity of Differentiated NG-108 Cells Through σ1R/IPR1 Complex.

Cell Mol Neurobiol

Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, 84505, Bratislava, Slovakia.

Published: January 2018

AI Article Synopsis

Article Abstract

Haloperidol is an antipsychotic agent that primarily acts as an antagonist of D2 dopamine receptors. Besides other receptor systems, it targets sigma 1 receptors (σ1Rs) and inositol 1,4,5-trisphosphate receptors (IPRs). Aim of this work was to investigate possible changes in IPRs and σ1Rs resulting from haloperidol treatment and to propose physiological consequences in differentiated NG-108 cells, i.e., effect on cellular plasticity. Haloperidol treatment resulted in up-regulation of both type 1 IPRs (IPR1s) and σ1Rs at mRNA and protein levels. Haloperidol treatment did not alter expression of other types of IPRs. Calcium release from endoplasmic reticulum (ER) mediated by increased amount of IPR1s elevated cytosolic calcium and generated ER stress. IPR1s were bound to σ1Rs, and translocation of this complex from ER to nucleus occurred in the group of cells treated with haloperidol, which was followed by increased nuclear calcium levels. Haloperidol-induced changes in cytosolic, reticular, and nuclear calcium levels were similar when specific σ1 blocker -BD 1047- was used. Changes in calcium levels in nucleus, ER, and cytoplasm might be responsible for alterations in cellular plasticity, because length of neurites increased and number of neurites decreased in haloperidol-treated differentiated NG-108 cells.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775985PMC
http://dx.doi.org/10.1007/s10571-017-0524-yDOI Listing

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