Antipsychotic Induced Alteration of Growth and Proteome of Rat Neural Stem Cells

Neural stem cells (NSCs) play a crucial role in the development and maturation of the central nervous system and therefore have the potential to target by therapeutic agents for a wide variety of diseases including neurodegenerative and neuropsychiatric illnesses. It has been suggested that antipsychotic drugs have significant effects on NSC activities. However, the molecular mechanisms underlying antipsychotic-induced changes of NSC activities, particularly growth and protein expression, are largely unknown. NSCs were treated with either haloperidol (HD; 3 μM), risperidone (RS; 3 μM) or vehicle (DMSO) for 96 h. Protein expression profiles were studied through a proteomics approach. RS promoted and HD inhibited the growth of NSCs. Proteomics analysis revealed that 15 protein spots identified as 12 unique proteins in HD-, and 20 protein spots identified as 14 proteins in RS-treated groups, were differentially expressed relative to control. When these identified proteins were compared between the two drug-treated groups, 2 proteins overlapped leaving 10 HD-specific and 12 RS-specific proteins. Further comparison of the overlapped altered proteins of 96 h treatment with the neuroleptics-induced overlapped proteins at 24 h time interval (Kashem et al. 40] in Neurochem Int 55:558-565, 2009) suggested that overlapping altered proteins expression at 24 h was decreased (17 proteins i.e. 53 % of total expressed proteins) with the increase of time (96 h) (2 proteins; 8 % of total expressed proteins). This result indicated that at early stage both drugs showed common mode of action but the action was opposite to each other while administration was prolonged. The opposite morphological pattern of cellular growth at 96 h has been associated with dominant expression of oxidative stress and apoptosis cascades in HD, and activation of growth regulating metabolic pathways in RS treated cells. These results may explain RS induced repairing of neural damage caused by a wide variety of neural diseases including schizophrenia.