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Effects of typical (haloperidol) and atypical (risperidone) antipsychotic agents on protein expression in rat neural stem cells.

Abstract：

: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.

journal_name

Neurochem Int

journal_title

Neurochemistry international

authors

Kashem MA,Ummehany R,Ukai W,Hashimoto E,Saito T,Mcgregor IS,Matsumoto I

doi

10.1016/j.neuint.2009.05.007

subject

Has Abstract

pub_date

2009-12-01 00:00:00

pages

558-65

issue

7

eissn

0197-0186

issn

1872-9754

pii

S0197-0186(09)00171-5

journal_volume

55

pub_type

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