Neural stem cells (NSCs) play a crucial role in the development and maturation of the
central nervous system. Recently studies suggest that
antipsychotic drugs regulate the activities of NSCs. However, the molecular mechanisms underlying antipsychotic-induced changes of the activity of NSCs, particularly
protein expression, are still unknown. We studied the growth and
protein expression in
haloperidol (HD) and
risperidone (RS) treated rat NSCs. The treatment with RS (3microM) or HD (3microM) had no effect on morphology of NSCs after 24h, but significantly promotes or inhibits the differentiation of NSCs after a 96h of treatment.
2-DE based
proteomics was performed at 24h, a stage before
phenotypic expression of NSCs.
Gel image analysis revealed that 30 protein spots in HD- and 60 spots in RS-treated groups were differentially regulated in their expression compared to control group (p<0.05;
ANOVA). When these spots were compared between the two drug-treated groups, 23 spots overlapped leaving 7 HD-specific and 37 RS-specific spots. Of these 67 spots, 32 different proteins were identified. The majority of the differentially regulated proteins were classified into several
functional groups, such as
cytoskeletal,
calcium regulating protein,
metabolism,
signal transduction and proteins related to
oxidative stress. Our data shows that atypical RS expressed more proteins than typical HD, and these results might explain the molecular mechanisms underlying the different effects of both
drugs on NSCs activities as described above. Identified proteins in this experiment may be useful in future studies of NSCs differentiation and/or understanding in molecular mechanisms of different
neural diseases including schizophenia.
