Antipsychotic modulation of stem cells

Sapporo, Japan –

Patients with schizophrenia are usually treated with antipsychotic drugs. Typical or atypical antipsychotics such as clozapine and olanzapine have been utilized with various degrees of success. The mechanisms of actions of these drugs are not completely known, although the majority do have dopamine modulatory activity.

In a recent publication (Kurosawa et al. Olanzapine potentiates neuronal survival and neural stem cell differentiation: regulation of endoplasmic reticulum stress response proteins. J Neural Transm. 2007 Jun 8) the possibility of the atypical antipsychotic olanzapine mediating neuroprotective effects at the level of neural progenitor cells is discussed.

The authors describe previous studies in which various neural structures are known to reduce in volume during the course of a schizophrenic’s lifetime. Furthermore, they discuss that various antipsychotics actually inhibit reduction in brain volume.

Experimentally, it was demonstrated that olanzapine products neurons from thapsigargin induced injury at the level of cell death. Additionally, the authors demonstrated that olanzapine blocks the ability of low dose thapsigarin to inhibit differentiation of neural stem cells into neurons. Mechanistically, olanzapine appears to act by decreasing stress conditions in the endoplasmic reticulum through suppressing ER chaperones such as GRP78.

If indeed various atypical antipsychotics can modulate stress in stem cells, they may have play a future role in combination with various exogenous and endogenous stem cell therapies.