Neural stem cell sex dimorphism in aromatase (CYP19) expression: a basis for differential neural fate

Jay Waldron1, Althea McCourty1, Laurent Lecanu1,21The Research Institute of the McGill University Health Centre, Montreal, Canada; 2Department of Medicine, McGill University, Quebec, CanadaPurpose: Neural stem cell (NSC) transplantation and pharmacologic activation of endogenous neurogenesis are two...

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Autores principales:	Jay Waldron, Althea McCourty, Laurent Lecanu
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2010
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/8397a9d73f4547c68dc3941183b14be2
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spelling	oai:doaj.org-article:8397a9d73f4547c68dc3941183b14be22021-12-02T05:55:32ZNeural stem cell sex dimorphism in aromatase (CYP19) expression: a basis for differential neural fate1178-6957https://doaj.org/article/8397a9d73f4547c68dc3941183b14be22010-11-01T00:00:00Zhttp://www.dovepress.com/neural-stem-cell-sex-dimorphism-in-aromatase-cyp19-expression-a-basis--a5712https://doaj.org/toc/1178-6957Jay Waldron1, Althea McCourty1, Laurent Lecanu1,21The Research Institute of the McGill University Health Centre, Montreal, Canada; 2Department of Medicine, McGill University, Quebec, CanadaPurpose: Neural stem cell (NSC) transplantation and pharmacologic activation of endogenous neurogenesis are two approaches that trigger a great deal of interest as brain repair strategies. However, the success rate of clinical attempts using stem cells to restore neurologic functions altered either after traumatic brain injury or as a consequence of neurodegenerative disease remains rather disappointing. This suggests that factors affecting the fate of grafted NSCs are largely understudied and remain to be characterized. We recently reported that aging differentially affects the neurogenic properties of male and female NSCs. Although the sex steroids androgens and estrogens participate in the regulation of neurogenesis, to our knowledge, research on how gender-based differences affect the capacity of NSCs to differentiate and condition their neural fate is lacking. In the present study, we explored further the role of cell sex as a determining factor of the neural fate followed by differentiating NSCs and its relationship with a potential differential expression of aromatase (CYP19), the testosterone-metabolizing enzyme.Results: Using NSCs isolated from the subventricular zone of three-month-old male and female Long-Evans rats and maintained as neurospheres, we showed that differentiation triggered by retinoic acid resulted in a neural phenotype that depends on cell sex. Differentiated male NSCs mainly expressed markers of neuronal fate, including &szlig;III-tubulin, microtubule associated protein 2, growth-associated protein 43, and doublecortin. In contrast, female NSCs essentially expressed the astrocyte marker glial fibrillary acidic protein. Quantification of the expression of aromatase showed a very low level of expression in undifferentiated female NSCs, whereas aromatase expression in male NSCs was 14-fold greater than the female level.Conclusion: Our results confirm our previous data that the neural phenotype acquired by differentiating NSCs largely depends on cell sex, and that differential expression of aromatase in undifferentiated NSCs might contribute to this sex-based dimorphism. Although still preliminary, our discovery may have clinical application in the development of future brain repair strategies.Keywords: neuroregenerative medicine, brain repair strategy, sex dimorphism, aromatase, adult stem cells Jay WaldronAlthea McCourtyLaurent LecanuDove Medical PressarticleCytologyQH573-671ENStem Cells and Cloning: Advances and Applications, Vol 2010, Iss default, Pp 175-182 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Jay Waldron Althea McCourty Laurent Lecanu Neural stem cell sex dimorphism in aromatase (CYP19) expression: a basis for differential neural fate
description	Jay Waldron1, Althea McCourty1, Laurent Lecanu1,21The Research Institute of the McGill University Health Centre, Montreal, Canada; 2Department of Medicine, McGill University, Quebec, CanadaPurpose: Neural stem cell (NSC) transplantation and pharmacologic activation of endogenous neurogenesis are two approaches that trigger a great deal of interest as brain repair strategies. However, the success rate of clinical attempts using stem cells to restore neurologic functions altered either after traumatic brain injury or as a consequence of neurodegenerative disease remains rather disappointing. This suggests that factors affecting the fate of grafted NSCs are largely understudied and remain to be characterized. We recently reported that aging differentially affects the neurogenic properties of male and female NSCs. Although the sex steroids androgens and estrogens participate in the regulation of neurogenesis, to our knowledge, research on how gender-based differences affect the capacity of NSCs to differentiate and condition their neural fate is lacking. In the present study, we explored further the role of cell sex as a determining factor of the neural fate followed by differentiating NSCs and its relationship with a potential differential expression of aromatase (CYP19), the testosterone-metabolizing enzyme.Results: Using NSCs isolated from the subventricular zone of three-month-old male and female Long-Evans rats and maintained as neurospheres, we showed that differentiation triggered by retinoic acid resulted in a neural phenotype that depends on cell sex. Differentiated male NSCs mainly expressed markers of neuronal fate, including &szlig;III-tubulin, microtubule associated protein 2, growth-associated protein 43, and doublecortin. In contrast, female NSCs essentially expressed the astrocyte marker glial fibrillary acidic protein. Quantification of the expression of aromatase showed a very low level of expression in undifferentiated female NSCs, whereas aromatase expression in male NSCs was 14-fold greater than the female level.Conclusion: Our results confirm our previous data that the neural phenotype acquired by differentiating NSCs largely depends on cell sex, and that differential expression of aromatase in undifferentiated NSCs might contribute to this sex-based dimorphism. Although still preliminary, our discovery may have clinical application in the development of future brain repair strategies.Keywords: neuroregenerative medicine, brain repair strategy, sex dimorphism, aromatase, adult stem cells
format	article
author	Jay Waldron Althea McCourty Laurent Lecanu
author_facet	Jay Waldron Althea McCourty Laurent Lecanu
author_sort	Jay Waldron
title	Neural stem cell sex dimorphism in aromatase (CYP19) expression: a basis for differential neural fate
title_short	Neural stem cell sex dimorphism in aromatase (CYP19) expression: a basis for differential neural fate
title_full	Neural stem cell sex dimorphism in aromatase (CYP19) expression: a basis for differential neural fate
title_fullStr	Neural stem cell sex dimorphism in aromatase (CYP19) expression: a basis for differential neural fate
title_full_unstemmed	Neural stem cell sex dimorphism in aromatase (CYP19) expression: a basis for differential neural fate
title_sort	neural stem cell sex dimorphism in aromatase (cyp19) expression: a basis for differential neural fate
publisher	Dove Medical Press
publishDate	2010
url	https://doaj.org/article/8397a9d73f4547c68dc3941183b14be2
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Neural stem cell sex dimorphism in aromatase (CYP19) expression: a basis for differential neural fate

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