Limited influence of olanzapine on adult forebrain neural precursors in vitro.
We evaluated the activity of the atypical antipsychotic drug olanzapine on differentiation and gene expression in adult neural precursor cells in vitro. Neural precursors obtained from forebrain subventricular zone (SVZ)-derived neurospheres express a subset (13/24) of receptors known to bind olanzapine at high to intermediate affinities; in contrast, all 24 are expressed in the SVZ. In the presence of 10 nM, 100 nM or 1 microM olanzapine, there is no significant change in the frequency of oligodendrocytes, neurons, GABAergic neurons and astrocytes generated from neurosphere precursors. In parallel, there is no apparent change in cell proliferation in response to olanzapine, based upon bromodeoxyuridine incorporation. There are no major changes in cytological differentiation in response to the drug; however, at one concentration (10 nM) there is a small but statistically significant increase in the size of glial fibrillary acidic protein-labeled astrocytes derived from neurosphere precursors. In addition, olanzapine apparently modulates expression of one serotonin receptor -- 5HT2A -- in differentiating neurosphere cultures; however, it does not modify expression of several other receptors or schizophrenia vulnerability genes. Thus, olanzapine has a limited influence on differentiation and gene expression in adult neural precursor cells in vitro.
Councill
J H
JH
Department of Cell and Molecular Physiology, UNC Neuroscience Center, and Silvio M. Conte Center for Research in Mental Disorders, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
Tucker
E S
ES
Haskell
G T
GT
Maynard
T M
TM
Meechan
D W
DW
Hamer
R M
RM
Lieberman
J A
JA
LaMantia
A-S
AS
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002552:Cerebral Ventricles / Q000166:cytology / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D000077152:Olanzapine; D016548:Prosencephalon / Q000166:cytology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology
D001569:Benzodiazepines; D001973:Bromodeoxyuridine; D009419:Nerve Tissue Proteins; D000077152:Olanzapine; D012333:RNA, Messenger; D017367:Selective Serotonin Reuptake Inhibitors