Objectives: In the present study, we compared the atypical antipsychotic risperidone (0.01-10 μM) with the typical antipsychotic haloperidol (0.01-10 μM) regarding to different aspects such as glutamate uptake, glutamine synthetase (GS) activity, glutathione (GSH) content and intracellular reactive oxygen species (ROS) production in C6 astroglial cells.
Methods: C6 glial cells were cultured in DMEM (pH 7.4) supplemented with 5% serum at 37oC/5% CO2. Experiments were performed in absence or presence of risperidone in a range from 10 to 40 µM. Glutamate uptake was measured by addition of L-[2,3-3H] glutamate. Glutamine synthetase (GS) activity was measured by colorimetric assay, glutathione (GSH) levels were measured by fluorimetric assay. Glial marker S100B was measured by ELISA. Cell death was performed by propidium iodide uptake assay. Data were analyzed statistically by ANOVA followed by Tukey´s test. P < 0.05 was considered significant.
Results: Risperidone was able to induce a significantly increase on glutamate uptake (32%); GS activity (15%); GSH levels (58%) and S100B secretion (80%). In the presence of high doses of risperidone, C6 cells become stellate, with process-bearing cells and partial retraction of the cell body followed by detachment from the adhesion surface with no cell death. Lysophosphatidic acid, a specific positive regulator of the GTPase RhoA, prevented the effects of risperidone on cell morphology.
Conclusions: These data contribute to the available knowledge regarding to neural responses after antipsychotic-induced stimulus and it could give rise to important insights about how to promote brain rewiring in autism spectrum.