The pro-apoptotic ARTS/Sept4 protein is significantly reduced in post-mortem brains from schizophrenic patients

Yossi Gottfried; Asaf Rotem; Ehud Klein; Sarit Larisch

doi:10.1016/j.schres.2007.05.031

The pro-apoptotic ARTS/Sept4 protein is significantly reduced in post-mortem brains from schizophrenic patients

Yossi Gottfried, Asaf Rotem, Ehud Klein, Sarit Larisch

Research output: Contribution to journal › Article › peer-review

Abstract

Schizophrenic brains exhibit various neuro-pathological changes in size, volume and structure as compared to normal brains. These structural abnormalities could be the result of apoptotic cell death. ARTS/Sept4 protein plays an important role in induction and promotion of apoptosis. Though ARTS is highly expressed in the healthy human brain, most of tested schizophrenic brain samples showed no expression of ARTS protein. Specifically, using Western blot analysis with monoclonal anti-ARTS antibody we found that only 1 out of 14 schizophrenic samples (7%) showed a strong ARTS signal as compared to 10 out of 15 (66.6%) found in the normal controls group. Furthermore, using immunohistochemistry assay only 33.3% (5 of 15) (SE ± 12.5) of the schizophrenic patients samples showed any ARTS immunoreactivity as compared to (13 of 15) 87% (SE ± 9) of bipolar, (11 of 14) 78% (SE ± 11.3) of major depression and (10 of 14) 71% (SE ± 12.5) of normal controls. A four-fold reduction in apoptosis rate was measured in these schizophrenic samples as compared to average apoptosis rate found in all other samples. These data support the linkage between loss of ARTS expression and the loss of sensitivity towards apoptosis. Interestingly, levels of ARTS were significantly lower in male schizophrenic patients as compared to female schizophrenic patients, and males of all other control groups. We propose that ARTS may play an important role in the pathogenesis of schizophrenia and could be used as a marker for this disease.

Original language	English
Pages (from-to)	257-266
Number of pages	10
Journal	Schizophrenia Research
Volume	96
Issue number	1-3
DOIs	https://doi.org/10.1016/j.schres.2007.05.031
State	Published - Nov 2007
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by the generous funding from the National Alliance for Research on Schizophrenia and Depression (NARSAD) and from the Israel Science Foundation (ISF). Support from these agencies allowed payment for a full time researcher and a PhD. student that worked on this project and the materials and reagents needed to pursue the scientific experiments described in this manuscript. In addition we acknowledge the generous contribution of post-mortem frontal cortex brain sections supplied from the Stanley Foundation, that made this study possible.

Keywords

ARTS
Apoptosis
Frontal cortex
Neurons
Schizophrenia

ASJC Scopus subject areas

Psychiatry and Mental health
Biological Psychiatry

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10.1016/j.schres.2007.05.031

Cite this

@article{6525295c51454e619bd9bca1255acd5a,

title = "The pro-apoptotic ARTS/Sept4 protein is significantly reduced in post-mortem brains from schizophrenic patients",

abstract = "Schizophrenic brains exhibit various neuro-pathological changes in size, volume and structure as compared to normal brains. These structural abnormalities could be the result of apoptotic cell death. ARTS/Sept4 protein plays an important role in induction and promotion of apoptosis. Though ARTS is highly expressed in the healthy human brain, most of tested schizophrenic brain samples showed no expression of ARTS protein. Specifically, using Western blot analysis with monoclonal anti-ARTS antibody we found that only 1 out of 14 schizophrenic samples (7%) showed a strong ARTS signal as compared to 10 out of 15 (66.6%) found in the normal controls group. Furthermore, using immunohistochemistry assay only 33.3% (5 of 15) (SE ± 12.5) of the schizophrenic patients samples showed any ARTS immunoreactivity as compared to (13 of 15) 87% (SE ± 9) of bipolar, (11 of 14) 78% (SE ± 11.3) of major depression and (10 of 14) 71% (SE ± 12.5) of normal controls. A four-fold reduction in apoptosis rate was measured in these schizophrenic samples as compared to average apoptosis rate found in all other samples. These data support the linkage between loss of ARTS expression and the loss of sensitivity towards apoptosis. Interestingly, levels of ARTS were significantly lower in male schizophrenic patients as compared to female schizophrenic patients, and males of all other control groups. We propose that ARTS may play an important role in the pathogenesis of schizophrenia and could be used as a marker for this disease.",

keywords = "ARTS, Apoptosis, Frontal cortex, Neurons, Schizophrenia",

author = "Yossi Gottfried and Asaf Rotem and Ehud Klein and Sarit Larisch",

note = "Funding Information: This work was supported by the generous funding from the National Alliance for Research on Schizophrenia and Depression (NARSAD) and from the Israel Science Foundation (ISF). Support from these agencies allowed payment for a full time researcher and a PhD. student that worked on this project and the materials and reagents needed to pursue the scientific experiments described in this manuscript. In addition we acknowledge the generous contribution of post-mortem frontal cortex brain sections supplied from the Stanley Foundation, that made this study possible. ",

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AU - Klein, Ehud

AU - Larisch, Sarit

N1 - Funding Information: This work was supported by the generous funding from the National Alliance for Research on Schizophrenia and Depression (NARSAD) and from the Israel Science Foundation (ISF). Support from these agencies allowed payment for a full time researcher and a PhD. student that worked on this project and the materials and reagents needed to pursue the scientific experiments described in this manuscript. In addition we acknowledge the generous contribution of post-mortem frontal cortex brain sections supplied from the Stanley Foundation, that made this study possible.

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N2 - Schizophrenic brains exhibit various neuro-pathological changes in size, volume and structure as compared to normal brains. These structural abnormalities could be the result of apoptotic cell death. ARTS/Sept4 protein plays an important role in induction and promotion of apoptosis. Though ARTS is highly expressed in the healthy human brain, most of tested schizophrenic brain samples showed no expression of ARTS protein. Specifically, using Western blot analysis with monoclonal anti-ARTS antibody we found that only 1 out of 14 schizophrenic samples (7%) showed a strong ARTS signal as compared to 10 out of 15 (66.6%) found in the normal controls group. Furthermore, using immunohistochemistry assay only 33.3% (5 of 15) (SE ± 12.5) of the schizophrenic patients samples showed any ARTS immunoreactivity as compared to (13 of 15) 87% (SE ± 9) of bipolar, (11 of 14) 78% (SE ± 11.3) of major depression and (10 of 14) 71% (SE ± 12.5) of normal controls. A four-fold reduction in apoptosis rate was measured in these schizophrenic samples as compared to average apoptosis rate found in all other samples. These data support the linkage between loss of ARTS expression and the loss of sensitivity towards apoptosis. Interestingly, levels of ARTS were significantly lower in male schizophrenic patients as compared to female schizophrenic patients, and males of all other control groups. We propose that ARTS may play an important role in the pathogenesis of schizophrenia and could be used as a marker for this disease.

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The pro-apoptotic ARTS/Sept4 protein is significantly reduced in post-mortem brains from schizophrenic patients

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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