Journal Article

Effects of antipsychotics, haloperidol and olanzapine, on the expression of apoptosis-related genes in mouse mHippoE-2 cells and rat hippocampus

Tillinger, Andrej, Osacka, Jana, Kiss, Alexander, Bacova, Zuzana

2023

Overview

Modified levels of pro- (caspase3, Bax) and anti-apoptotic (Bcl-2) regulatory proteins have been detected in certain brain areas of schizophrenic patients indicating a possible dysregulation of apoptosis. In the present study, effects of antipsychotics, haloperidol (HAL) and olanzapine (OLA), on the gene expression of caspase3 ( ), and were studied in mouse hippocampal mHippoE-2 cell line and in the hippocampus of MK-801 animal schizophrenia model with the aim to provide evidence that antipsychotics may affect the activity of apoptosis-related markers. mHippoE-2 cells were incubated with MK-801 (20 µM), HAL (10 µM), and OLA (10 µM) alone or combined, MK-801+HAL/OLA, for 24, 48, and 72 h. Male Sprague Dawley rats were injected with saline or MK-801 (0.5 mg/kg) for 6 days and since the 7th day, they were treated with vehicle (VEH), HAL (1 mg/kg) or OLA (2 mg/kg) for the next 7 days. The , and gene expression in mHippoE-2 cells and rat hippocampus was measured by RT-PCR. In mHippoE-2 cells, gene expression was increased by MK-801 and OLA treatments alone for 48 h, HAL treatment alone for 24 and 72 h, and co-treatment with MK-801+OLA for 24 and 72 h compared to controls. HAL and OLA suppressed the stimulatory effect of MK-801 on mRNA levels in cells after 48 h of incubation. mRNA levels in mHippoE-2 cells were decreased after HAL treatment for 24 and 48 h, and also after co-treatment with MK-801+HAL for 72 h. , MK-801 decreased mRNA levels of both pro-apoptotic markers, and , in hippocampus of VEH-treated rats and mRNA levels in hippocampus of HAL-treated animals. OLA reversed the inhibitory effect of MK-801 on expression in the VEH-treated animals. Neither MK-801 nor antipsychotics induced changes in the gene expression of anti-apoptotic marker in mHippoE-2 cells as well as hippocampus of rats. The results of the present study demonstrate that antipsychotics, HAL and OLA, may affect mRNA levels of pro-apoptotic markers in hippocampal cells , but not . The obtained data do not clearly support the assumed potentiating role of MK-801 in inducing apoptosis in specific brain areas and a possible protective role of antipsychotics against induction of apoptosis. The obtained data may contribute to a deeper insight into the neurodevelopmental changes connected with schizophrenia.

• Publisher: Sciendo,De Gruyter Brill Sp. z o.o., Paradigm Publishing Services
• Subject: Antipsychotics / Apoptosis / apoptosis-related gens / Gene expression / haloperidol / hippocampus / olanzapine / Psychotropic drugs / Schizophrenia