Olanzapine potentiates neuronal survival and neural stem cell differentiation: regulation of endoplasmic reticulum stress response proteins
| Autor: | Wataru Ukai, S. Saito, Toshikazu Saito, S. Kurosawa, Sadamu Toki, Eri Hashimoto |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Thapsigargin
medicine.drug_class Cell Survival Atypical antipsychotic Biology Pharmacology Endoplasmic Reticulum Neuroprotection chemistry.chemical_compound Benzodiazepines Pregnancy medicine Animals Rats Wistar Biological Psychiatry Cells Cultured Heat-Shock Proteins Neurons Endoplasmic reticulum Stem Cells Cell Differentiation Drug Synergism Typical antipsychotic Neural stem cell Rats Psychiatry and Mental health nervous system Neurology chemistry Olanzapine biology.protein Unfolded protein response Female Neurology (clinical) Neurotrophin Antipsychotic Agents |
| Zdroj: | Journal of neural transmission (Vienna, Austria : 1996). 114(9) |
| ISSN: | 1435-1463 |
| Popis: | Recent clinical neuroimaging studies have suggested that morphological brain changes occur and progress in the course of schizophrenia. Although the neurogenetic and neurotrophic effects of antipsychotics are considered to contribute to the prevention of reduction in brain volume, the cellular molecular mechanisms of action of antipsychotics have not yet been elucidated. We examined the effects of antipsychotics on the endoplasmic reticulum (ER) stress-induced damages of neurons and neural stem cells (NSCs) using cultured cells. In the neuronal cultures, the atypical antipsychotic olanzapine protected neurons from thapsigargin (1 microM)-induced injury. It was observed that a low concentration of thapsigargin (10 nM) that did not affect the neuronal survival could reduce neuronal differentiation of cultured NSCs, suggesting a role of ER stress in the differentiation function of NSCs. Treatment with olanzapine increased the neuronal differentiation suppressed by the exposure to thapsigargin (10 nM). The thapsigargin-induced ER chaperones, GRP78, which indicate the ER stress condition of the cell, were decreased by the treatment with the atypical antipsychotics olanzapine and quetiapine but not by the typical antipsychotic haloperidol. These results indicate that the amelioration of ER-stress might be involved in the cellular mechanisms of atypical antipsychotics to produce neuroprotective and neurogenetic actions in neurons and NSCs, suggesting potential roles of these drugs for treatment of schizophrenia. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink