<abstract xmlns="http://www.w3.org/1999/xhtml">

<bold>Objective.</bold> 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 (<italic>casp3</italic>), <italic>Bax</italic> and <italic>Bcl-2</italic> were studied <italic>in vitro</italic> in mouse hippocampal mHippoE-2 cell line and <italic>in vivo</italic> 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.
<bold>Methods.</bold> 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 <italic>casp3</italic>, <italic>Bax</italic> and <italic>Bcl-2</italic> gene expression in mHippoE-2 cells and rat hippocampus was measured by RT-PCR.
<bold>Results.</bold> In mHippoE-2 cells, <italic>casp3</italic> 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 <italic>casp3</italic> mRNA levels in cells after 48 h of incubation. <italic>Bax</italic> 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. <italic>In vivo</italic>, MK-801 decreased mRNA levels of both pro-apoptotic markers, <italic>casp3</italic> and <italic>Bax</italic>, in hippocampus of VEH-treated rats and <italic>Bax</italic> mRNA levels in hippocampus of HAL-treated animals. OLA reversed the inhibitory effect of MK-801 on <italic>casp3</italic> expression in the VEH-treated animals. Neither MK-801 nor antipsychotics induced changes in the gene expression of anti-apoptotic marker <italic>Bcl-2</italic> in mHippoE-2 cells as well as hippocampus of rats.
<bold>Conclusions.</bold> The results of the present study demonstrate that antipsychotics, HAL and OLA, may affect mRNA levels of pro-apoptotic markers in hippocampal cells <italic>in vitro</italic>, but not <italic>in vivo</italic>. 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.
</abstract>

Objective. 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 (casp3), Bax and Bcl-2 were studied in vitro in mouse hippocampal mHippoE-2 cell line and in vivo 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.
Methods. 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 casp3, Bax and Bcl-2 gene expression in mHippoE-2 cells and rat hippocampus was measured by RT-PCR.
Results. In mHippoE-2 cells, casp3 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 casp3 mRNA levels in cells after 48 h of incubation. Bax 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. In vivo, MK-801 decreased mRNA levels of both pro-apoptotic markers, casp3 and Bax, in hippocampus of VEH-treated rats and Bax mRNA levels in hippocampus of HAL-treated animals. OLA reversed the inhibitory effect of MK-801 on casp3 expression in the VEH-treated animals. Neither MK-801 nor antipsychotics induced changes in the gene expression of anti-apoptotic marker Bcl-2 in mHippoE-2 cells as well as hippocampus of rats.
Conclusions. The results of the present study demonstrate that antipsychotics, HAL and OLA, may affect mRNA levels of pro-apoptotic markers in hippocampal cells in vitro, but not in vivo. 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.

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

Endocrine Regulations

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Objective. Modified levels of pro- (caspase3, Bax) and anti-apoptotic (Bcl-2) regulatory proteins have been detected in certain brain areas of schizophrenic...

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

Published Online: Aug 10, 2023

Page range: 152 - 161

DOI: https://doi.org/10.2478/enr-2023-0019

Keywords
schizophrenia, hippocampus, haloperidol, olanzapine, apoptosis, apoptosis-related gens

© 2023 Jana Osacka et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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

Published Online: Aug 10, 2023

Page range: 152 - 161

DOI: https://doi.org/10.2478/enr-2023-0019

Keywordsschizophrenia, hippocampus, haloperidol, olanzapine, apoptosis, apoptosis-related gens

© 2023 Jana Osacka et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Keywords
schizophrenia, hippocampus, haloperidol, olanzapine, apoptosis, apoptosis-related gens