Involvement of stat3 in mouse brain development and sexual dimorphism: A proteomics approach

Fabio Di Domenico; Gabriella Casalena; Rukhsana Sultana; Jian Cai; William M. Pierce; Marzia Perluigi; Chiara Cini; Alessandra Baracca; Giancarlo Solaini; Giorgio Lenaz; Jia Jia; Suzan Dziennis; Stephanie J. Murphy; Nabil J. Alkayed; D. Allan Butterfield

doi:10.1016/j.brainres.2010.09.074

Involvement of stat3 in mouse brain development and sexual dimorphism: A proteomics approach

Fabio Di Domenico, Gabriella Casalena, Rukhsana Sultana, Jian Cai, William M. Pierce, Marzia Perluigi, Chiara Cini, Alessandra Baracca, Giancarlo Solaini, Giorgio Lenaz, Jia Jia, Suzan Dziennis, Stephanie J. Murphy, Nabil J. Alkayed, D. Allan Butterfield

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

18 Scopus citations

Abstract

Although the role of STAT3 in cell physiology and tissue development has been largely investigated, its involvement in the development and maintenance of nervous tissue and in the mechanisms of neuroprotection is not yet known. The potentially wide range of STAT3 activities raises the question of tissue- and gender-specificity as putative mechanisms of regulation. To explore the function of STAT3 in the brain and the hypothesis of a gender-linked modulation of STAT3, we analyzed a neuron-specific STAT3 knockout mouse model investigating the influence of STAT3 activity in brain protein expression pattern in both males and females in the absence of neurological insult. We performed a proteomic study aimed to reveal the molecular pathways directly or indirectly controlled by STAT3 underscoring its role in brain development and maintenance. We identified several proteins, belonging to different neuronal pathways such as energy metabolism or synaptic transmission, controlled by STAT3 that confirm its crucial role in brain development and maintenance. Moreover, we investigated the different processes that could contribute to the sexual dimorphic behavior observed in the incidence of neurological and mental disease. Interestingly both STAT3 KO and gender factors influence the expression of several mitochondrial proteins conferring to mitochondrial activity high importance in the regulation of brain physiology and conceivable relevance as therapeutic target.

Original language	English
Pages (from-to)	1-12
Number of pages	12
Journal	Brain Research
Volume	1362
DOIs	https://doi.org/10.1016/j.brainres.2010.09.074
State	Published - Nov 29 2010

Bibliographical note

Funding Information:
The hypothesis of an unstable equilibrium redox in males STAT3 KO is supported by the decreased expression of Prdx6. HDH is a mitochondrial membrane enzyme involved in the NAD-dependent metabolism of ketone bodies. Our data showed that in STAT3 KO male brain the expression of both PDH and HDH is severely down regulated, thus leading to a condition in which mitochondria could be deprived of substrates for TCA cycle. Therefore, in males the knock out of STAT3 gene likely results in a deficit in the mitochondrial capacity to adapt to changes in substrates availability, which could make them more vulnerable upon stress inducing events.

Keywords

Neuron-Specific STAT3
Proteomics
Sexual dimorphism

ASJC Scopus subject areas

General Neuroscience
Molecular Biology
Clinical Neurology
Developmental Biology

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10.1016/j.brainres.2010.09.074

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Di Domenico, F., Casalena, G., Sultana, R., Cai, J., Pierce, W. M., Perluigi, M., Cini, C., Baracca, A., Solaini, G., Lenaz, G., Jia, J., Dziennis, S., Murphy, S. J., Alkayed, N. J., & Butterfield, D. A. (2010). Involvement of stat3 in mouse brain development and sexual dimorphism: A proteomics approach. Brain Research, 1362, 1-12. https://doi.org/10.1016/j.brainres.2010.09.074

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title = "Involvement of stat3 in mouse brain development and sexual dimorphism: A proteomics approach",

abstract = "Although the role of STAT3 in cell physiology and tissue development has been largely investigated, its involvement in the development and maintenance of nervous tissue and in the mechanisms of neuroprotection is not yet known. The potentially wide range of STAT3 activities raises the question of tissue- and gender-specificity as putative mechanisms of regulation. To explore the function of STAT3 in the brain and the hypothesis of a gender-linked modulation of STAT3, we analyzed a neuron-specific STAT3 knockout mouse model investigating the influence of STAT3 activity in brain protein expression pattern in both males and females in the absence of neurological insult. We performed a proteomic study aimed to reveal the molecular pathways directly or indirectly controlled by STAT3 underscoring its role in brain development and maintenance. We identified several proteins, belonging to different neuronal pathways such as energy metabolism or synaptic transmission, controlled by STAT3 that confirm its crucial role in brain development and maintenance. Moreover, we investigated the different processes that could contribute to the sexual dimorphic behavior observed in the incidence of neurological and mental disease. Interestingly both STAT3 KO and gender factors influence the expression of several mitochondrial proteins conferring to mitochondrial activity high importance in the regulation of brain physiology and conceivable relevance as therapeutic target.",

keywords = "Neuron-Specific STAT3, Proteomics, Sexual dimorphism",

author = "{Di Domenico}, Fabio and Gabriella Casalena and Rukhsana Sultana and Jian Cai and Pierce, {William M.} and Marzia Perluigi and Chiara Cini and Alessandra Baracca and Giancarlo Solaini and Giorgio Lenaz and Jia Jia and Suzan Dziennis and Murphy, {Stephanie J.} and Alkayed, {Nabil J.} and Butterfield, {D. Allan}",

note = "Funding Information: The hypothesis of an unstable equilibrium redox in males STAT3 KO is supported by the decreased expression of Prdx6. HDH is a mitochondrial membrane enzyme involved in the NAD-dependent metabolism of ketone bodies. Our data showed that in STAT3 KO male brain the expression of both PDH and HDH is severely down regulated, thus leading to a condition in which mitochondria could be deprived of substrates for TCA cycle. Therefore, in males the knock out of STAT3 gene likely results in a deficit in the mitochondrial capacity to adapt to changes in substrates availability, which could make them more vulnerable upon stress inducing events. ",

year = "2010",

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doi = "10.1016/j.brainres.2010.09.074",

language = "English",

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T2 - A proteomics approach

AU - Di Domenico, Fabio

AU - Casalena, Gabriella

AU - Sultana, Rukhsana

AU - Cai, Jian

AU - Pierce, William M.

AU - Perluigi, Marzia

AU - Cini, Chiara

AU - Baracca, Alessandra

AU - Solaini, Giancarlo

AU - Lenaz, Giorgio

AU - Jia, Jia

AU - Dziennis, Suzan

AU - Murphy, Stephanie J.

AU - Alkayed, Nabil J.

AU - Butterfield, D. Allan

N1 - Funding Information: The hypothesis of an unstable equilibrium redox in males STAT3 KO is supported by the decreased expression of Prdx6. HDH is a mitochondrial membrane enzyme involved in the NAD-dependent metabolism of ketone bodies. Our data showed that in STAT3 KO male brain the expression of both PDH and HDH is severely down regulated, thus leading to a condition in which mitochondria could be deprived of substrates for TCA cycle. Therefore, in males the knock out of STAT3 gene likely results in a deficit in the mitochondrial capacity to adapt to changes in substrates availability, which could make them more vulnerable upon stress inducing events.

PY - 2010/11/29

Y1 - 2010/11/29

N2 - Although the role of STAT3 in cell physiology and tissue development has been largely investigated, its involvement in the development and maintenance of nervous tissue and in the mechanisms of neuroprotection is not yet known. The potentially wide range of STAT3 activities raises the question of tissue- and gender-specificity as putative mechanisms of regulation. To explore the function of STAT3 in the brain and the hypothesis of a gender-linked modulation of STAT3, we analyzed a neuron-specific STAT3 knockout mouse model investigating the influence of STAT3 activity in brain protein expression pattern in both males and females in the absence of neurological insult. We performed a proteomic study aimed to reveal the molecular pathways directly or indirectly controlled by STAT3 underscoring its role in brain development and maintenance. We identified several proteins, belonging to different neuronal pathways such as energy metabolism or synaptic transmission, controlled by STAT3 that confirm its crucial role in brain development and maintenance. Moreover, we investigated the different processes that could contribute to the sexual dimorphic behavior observed in the incidence of neurological and mental disease. Interestingly both STAT3 KO and gender factors influence the expression of several mitochondrial proteins conferring to mitochondrial activity high importance in the regulation of brain physiology and conceivable relevance as therapeutic target.

AB - Although the role of STAT3 in cell physiology and tissue development has been largely investigated, its involvement in the development and maintenance of nervous tissue and in the mechanisms of neuroprotection is not yet known. The potentially wide range of STAT3 activities raises the question of tissue- and gender-specificity as putative mechanisms of regulation. To explore the function of STAT3 in the brain and the hypothesis of a gender-linked modulation of STAT3, we analyzed a neuron-specific STAT3 knockout mouse model investigating the influence of STAT3 activity in brain protein expression pattern in both males and females in the absence of neurological insult. We performed a proteomic study aimed to reveal the molecular pathways directly or indirectly controlled by STAT3 underscoring its role in brain development and maintenance. We identified several proteins, belonging to different neuronal pathways such as energy metabolism or synaptic transmission, controlled by STAT3 that confirm its crucial role in brain development and maintenance. Moreover, we investigated the different processes that could contribute to the sexual dimorphic behavior observed in the incidence of neurological and mental disease. Interestingly both STAT3 KO and gender factors influence the expression of several mitochondrial proteins conferring to mitochondrial activity high importance in the regulation of brain physiology and conceivable relevance as therapeutic target.

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KW - Proteomics

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JO - Brain Research

JF - Brain Research

ER -

Involvement of stat3 in mouse brain development and sexual dimorphism: A proteomics approach

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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Cite this