International Meeting for Autism Research: Non-Neuronal Targets of Antipsychotics

Non-Neuronal Targets of Antipsychotics

Saturday, May 22, 2010
Franklin Hall B Level 4 (Philadelphia Marriott Downtown)
11:00 AM
C. Gottfried , Biochemistry, UFRGS, Porto Aelgre, Brazil
A. Quincozes-Santos , Biochemistry, UFRGS, Porto Aelgre, Brazil
L. D. Bobermin , Biochemistry, UFRGS, Porto Aelgre, Brazil
M. C. Leite , Biochemistry, UFRGS, Porto Aelgre, Brazil
R. T. Abib , Biochemistry, UFRGS, Porto Aelgre, Brazil
V. Bambini-Junior , Biochemistry, UFRGS, Porto Aelgre, Brazil
F. Zeidán-Chuliá , Biochemistry, UFRGS, Porto Aelgre, Brazil
R. Riesgo , Pediatrics, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, Brazil
C. A. Goncalves , Biochemistry, UFRGS, Porto Aelgre, Brazil
Background: Although classical and atypical antipsychotics may have different neurotoxical effects, their underlying mechanisms remain to be elucidated, especially regarding to neuroglial function. It still remained unclear which and to what extent is the specific effect exerted on glial cells upon neuroleptic treatment.

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.

See more of: Neurophysiology
See more of: Neurophysiology
See more of: Brain Structure & Function