In-depth quantitative proteomic characterization of organotypic hippocampal slice culture reveals sex-specific differences in biochemical pathways

Abstract Sex differences in the brain of mammals range from neuroarchitecture through cognition to cellular metabolism. The hippocampus, a structure mostly associated with learning and memory, presents high vulnerability to neurodegeneration and aging. Therefore, we explored basal sex-related differ...

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Autores principales: Simone Nardin Weis, Jaques Miranda F. Souza, Juliana Bender Hoppe, Marina Firmino, Manfred Auer, Nassim N. Ataii, Leonardo Assis da Silva, Mariana Maier Gaelzer, Caroline Peres Klein, Alan R. Mól, Consuelo M. R. de Lima, Diogo Onofre Souza, Christianne G. Salbego, Carlos André O. Ricart, Wagner Fontes, Marcelo Valle de Sousa
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/cfe2a9cf46204172b40da2ef677cf9aa
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spelling oai:doaj.org-article:cfe2a9cf46204172b40da2ef677cf9aa2021-12-02T10:48:13ZIn-depth quantitative proteomic characterization of organotypic hippocampal slice culture reveals sex-specific differences in biochemical pathways10.1038/s41598-021-82016-72045-2322https://doaj.org/article/cfe2a9cf46204172b40da2ef677cf9aa2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82016-7https://doaj.org/toc/2045-2322Abstract Sex differences in the brain of mammals range from neuroarchitecture through cognition to cellular metabolism. The hippocampus, a structure mostly associated with learning and memory, presents high vulnerability to neurodegeneration and aging. Therefore, we explored basal sex-related differences in the proteome of organotypic hippocampal slice culture, a major in vitro model for studying the cellular and molecular mechanisms related to neurodegenerative disorders. Results suggest a greater prevalence of astrocytic metabolism in females and significant neuronal metabolism in males. The preference for glucose use in glycolysis, pentose phosphate pathway and glycogen metabolism in females and high abundance of mitochondrial respiration subunits in males support this idea. An overall upregulation of lipid metabolism was observed in females. Upregulation of proteins responsible for neuronal glutamate and GABA synthesis, along with synaptic associated proteins, were observed in males. In general, the significant spectrum of pathways known to predominate in neurons or astrocytes, together with the well-known neuronal and glial markers observed, revealed sex-specific metabolic differences in the hippocampus. TEM qualitative analysis might indicate a greater presence of mitochondria at CA1 synapses in females. These findings are crucial to a better understanding of how sex chromosomes can influence the physiology of cultured hippocampal slices and allow us to gain insights into distinct responses of males and females on neurological diseases that present a sex-biased incidence.Simone Nardin WeisJaques Miranda F. SouzaJuliana Bender HoppeMarina FirminoManfred AuerNassim N. AtaiiLeonardo Assis da SilvaMariana Maier GaelzerCaroline Peres KleinAlan R. MólConsuelo M. R. de LimaDiogo Onofre SouzaChristianne G. SalbegoCarlos André O. RicartWagner FontesMarcelo Valle de SousaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Simone Nardin Weis
Jaques Miranda F. Souza
Juliana Bender Hoppe
Marina Firmino
Manfred Auer
Nassim N. Ataii
Leonardo Assis da Silva
Mariana Maier Gaelzer
Caroline Peres Klein
Alan R. Mól
Consuelo M. R. de Lima
Diogo Onofre Souza
Christianne G. Salbego
Carlos André O. Ricart
Wagner Fontes
Marcelo Valle de Sousa
In-depth quantitative proteomic characterization of organotypic hippocampal slice culture reveals sex-specific differences in biochemical pathways
description Abstract Sex differences in the brain of mammals range from neuroarchitecture through cognition to cellular metabolism. The hippocampus, a structure mostly associated with learning and memory, presents high vulnerability to neurodegeneration and aging. Therefore, we explored basal sex-related differences in the proteome of organotypic hippocampal slice culture, a major in vitro model for studying the cellular and molecular mechanisms related to neurodegenerative disorders. Results suggest a greater prevalence of astrocytic metabolism in females and significant neuronal metabolism in males. The preference for glucose use in glycolysis, pentose phosphate pathway and glycogen metabolism in females and high abundance of mitochondrial respiration subunits in males support this idea. An overall upregulation of lipid metabolism was observed in females. Upregulation of proteins responsible for neuronal glutamate and GABA synthesis, along with synaptic associated proteins, were observed in males. In general, the significant spectrum of pathways known to predominate in neurons or astrocytes, together with the well-known neuronal and glial markers observed, revealed sex-specific metabolic differences in the hippocampus. TEM qualitative analysis might indicate a greater presence of mitochondria at CA1 synapses in females. These findings are crucial to a better understanding of how sex chromosomes can influence the physiology of cultured hippocampal slices and allow us to gain insights into distinct responses of males and females on neurological diseases that present a sex-biased incidence.
format article
author Simone Nardin Weis
Jaques Miranda F. Souza
Juliana Bender Hoppe
Marina Firmino
Manfred Auer
Nassim N. Ataii
Leonardo Assis da Silva
Mariana Maier Gaelzer
Caroline Peres Klein
Alan R. Mól
Consuelo M. R. de Lima
Diogo Onofre Souza
Christianne G. Salbego
Carlos André O. Ricart
Wagner Fontes
Marcelo Valle de Sousa
author_facet Simone Nardin Weis
Jaques Miranda F. Souza
Juliana Bender Hoppe
Marina Firmino
Manfred Auer
Nassim N. Ataii
Leonardo Assis da Silva
Mariana Maier Gaelzer
Caroline Peres Klein
Alan R. Mól
Consuelo M. R. de Lima
Diogo Onofre Souza
Christianne G. Salbego
Carlos André O. Ricart
Wagner Fontes
Marcelo Valle de Sousa
author_sort Simone Nardin Weis
title In-depth quantitative proteomic characterization of organotypic hippocampal slice culture reveals sex-specific differences in biochemical pathways
title_short In-depth quantitative proteomic characterization of organotypic hippocampal slice culture reveals sex-specific differences in biochemical pathways
title_full In-depth quantitative proteomic characterization of organotypic hippocampal slice culture reveals sex-specific differences in biochemical pathways
title_fullStr In-depth quantitative proteomic characterization of organotypic hippocampal slice culture reveals sex-specific differences in biochemical pathways
title_full_unstemmed In-depth quantitative proteomic characterization of organotypic hippocampal slice culture reveals sex-specific differences in biochemical pathways
title_sort in-depth quantitative proteomic characterization of organotypic hippocampal slice culture reveals sex-specific differences in biochemical pathways
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/cfe2a9cf46204172b40da2ef677cf9aa
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