Assessing the impact of neuronal activityon the redox balance of neurons and glia

Detalhes bibliográficos
Autor(a) principal: Silva, Jéssica José Abreu da
Data de Publicação: 2022
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Texto Completo: http://hdl.handle.net/10773/36361
Resumo: Maintaining physiological variables at a set point is crucial to the organization and function of the nervous system. Homeostatic synaptic plasticity, also known as synaptic scaling, is a form of neuronal plasticity which responds to disrupted activity in a neural circuit by using negative feedback, allowing individual neurons to modify their overall firing rate. Due to its importance in homeostasis, its investigation is of the utmost relevance. Until now, there was no evidence of the role of synaptic scaling in the redox balance of neurons and their neighboring glia. In this work, the retina of the chick embryo is used as the experimental model, and neuronal activity is modulated: neurons are upscaled (increase in the firing rate due to chronic inactivity) or downscaled (decrease in the firing rate due to chronic overactivity), to assess the impact of this modulation on the redox balance of neurons and glia. We demonstrated that upscaling or downscaling altered the redox balance of neurons. More specifically, both changed the redox balance towards a more reduced state of the cytosol. This change in cytosolic redox state was accompanied by an increase in the membrane expression of the Sodium Vitamin C co-transporter 2 (SVCT2) without affecting the content of intracellular ascorbate, the reduced form of vitamin C. Neuronal downscaling also led to redox alterations in the Müller glia, but not neuronal upscaling. Moreover, since mitochondria are the major ROS-producing organelle and previous studies have reported its alteration in neuronal activity, its oxidative damage level was assessed. Our model showed no alteration in the mitochondrial status upon synaptic scaling.
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spelling Assessing the impact of neuronal activityon the redox balance of neurons and gliaRedox balanceNeuronal activityNeuronal plasticityGlial cellsVitamin CMaintaining physiological variables at a set point is crucial to the organization and function of the nervous system. Homeostatic synaptic plasticity, also known as synaptic scaling, is a form of neuronal plasticity which responds to disrupted activity in a neural circuit by using negative feedback, allowing individual neurons to modify their overall firing rate. Due to its importance in homeostasis, its investigation is of the utmost relevance. Until now, there was no evidence of the role of synaptic scaling in the redox balance of neurons and their neighboring glia. In this work, the retina of the chick embryo is used as the experimental model, and neuronal activity is modulated: neurons are upscaled (increase in the firing rate due to chronic inactivity) or downscaled (decrease in the firing rate due to chronic overactivity), to assess the impact of this modulation on the redox balance of neurons and glia. We demonstrated that upscaling or downscaling altered the redox balance of neurons. More specifically, both changed the redox balance towards a more reduced state of the cytosol. This change in cytosolic redox state was accompanied by an increase in the membrane expression of the Sodium Vitamin C co-transporter 2 (SVCT2) without affecting the content of intracellular ascorbate, the reduced form of vitamin C. Neuronal downscaling also led to redox alterations in the Müller glia, but not neuronal upscaling. Moreover, since mitochondria are the major ROS-producing organelle and previous studies have reported its alteration in neuronal activity, its oxidative damage level was assessed. Our model showed no alteration in the mitochondrial status upon synaptic scaling.Manter as variáveis fisiológicas homeostáticas é crucial para a organização e função do sistema nervoso. A plasticidade sináptica homeostática, também conhecida como ”synaptic scaling”, é uma forma de plasticidade neuronal que responde à atividade anormal em um circuito neural usando feedback negativo, permitindo que neurónios individuais modifiquem a sua taxa de disparo. Devido à sua importância na homeostasia, a sua investigação é de extrema relevância. Até agora não havia evidências do papel do “synaptic scaling” no equilíbrio redox dos neurónios e suas glias vizinhas. Neste trabalho, a retina do embrião de galinha é usada como modelo experimental e a atividade neuronal é modulada: os neurónios são “upscaled” (aumento nos disparos de potenciais de ação após inatividade prolongada) ou “downscaled” (diminuição dos disparos após hiperatividade crónica) para posterior avaliação do seu impacto no balanço redox de neurónios e glia. Demonstramos que tanto o upscaling quanto o downscaling alteraram o balanço redox dos neurónios. Mais especificamente, ambos alteraram o equilíbrio redox para um estado mais reduzido do citosol. Este aumento na redução das proteínas foi acompanhado com um aumento na expressão de membrana do co-transportador de sódio e vitamina C tipo 2 (SVCT2), sem afetar o conteúdo intracelular de ascorbato, a forma predominante e reduzida da vitamina C. O downscaling neuronal também levou a alterações no balanço redox na glia de Müller, mas tal não foi observado com o upscaling neuronal. Além disso, como as mitocôndrias são o principal organelo produtor de ROS, e estudos anteriores relataram sua alteração na atividade neuronal, seu nível de dano oxidativo foi avaliado. No nosso modelo, nenhuma alteração foi observada no estado mitocondrial face ao “synaptic scaling”.2024-12-26T00:00:00Z2022-12-20T00:00:00Z2022-12-20info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/36361engSilva, Jéssica José Abreu dainfo:eu-repo/semantics/embargoedAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-06T04:43:11Zoai:ria.ua.pt:10773/36361Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T14:17:58.372233Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Assessing the impact of neuronal activityon the redox balance of neurons and glia
title Assessing the impact of neuronal activityon the redox balance of neurons and glia
spellingShingle Assessing the impact of neuronal activityon the redox balance of neurons and glia
Silva, Jéssica José Abreu da
Redox balance
Neuronal activity
Neuronal plasticity
Glial cells
Vitamin C
title_short Assessing the impact of neuronal activityon the redox balance of neurons and glia
title_full Assessing the impact of neuronal activityon the redox balance of neurons and glia
title_fullStr Assessing the impact of neuronal activityon the redox balance of neurons and glia
title_full_unstemmed Assessing the impact of neuronal activityon the redox balance of neurons and glia
title_sort Assessing the impact of neuronal activityon the redox balance of neurons and glia
author Silva, Jéssica José Abreu da
author_facet Silva, Jéssica José Abreu da
author_role author
dc.contributor.author.fl_str_mv Silva, Jéssica José Abreu da
dc.subject.por.fl_str_mv Redox balance
Neuronal activity
Neuronal plasticity
Glial cells
Vitamin C
topic Redox balance
Neuronal activity
Neuronal plasticity
Glial cells
Vitamin C
description Maintaining physiological variables at a set point is crucial to the organization and function of the nervous system. Homeostatic synaptic plasticity, also known as synaptic scaling, is a form of neuronal plasticity which responds to disrupted activity in a neural circuit by using negative feedback, allowing individual neurons to modify their overall firing rate. Due to its importance in homeostasis, its investigation is of the utmost relevance. Until now, there was no evidence of the role of synaptic scaling in the redox balance of neurons and their neighboring glia. In this work, the retina of the chick embryo is used as the experimental model, and neuronal activity is modulated: neurons are upscaled (increase in the firing rate due to chronic inactivity) or downscaled (decrease in the firing rate due to chronic overactivity), to assess the impact of this modulation on the redox balance of neurons and glia. We demonstrated that upscaling or downscaling altered the redox balance of neurons. More specifically, both changed the redox balance towards a more reduced state of the cytosol. This change in cytosolic redox state was accompanied by an increase in the membrane expression of the Sodium Vitamin C co-transporter 2 (SVCT2) without affecting the content of intracellular ascorbate, the reduced form of vitamin C. Neuronal downscaling also led to redox alterations in the Müller glia, but not neuronal upscaling. Moreover, since mitochondria are the major ROS-producing organelle and previous studies have reported its alteration in neuronal activity, its oxidative damage level was assessed. Our model showed no alteration in the mitochondrial status upon synaptic scaling.
publishDate 2022
dc.date.none.fl_str_mv 2022-12-20T00:00:00Z
2022-12-20
2024-12-26T00:00:00Z
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