Age-Associated Upregulation of Glutamate Transporters and Glutamine Synthetase in Senescent Astrocytes In Vitro and in the Mouse and Human Hippocampus

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art_MATIAS_AgeAssociated_Upregulation_of_Glutamate_Transporters_and_Glutamine_Synthetase_.PDF (3.55 MB)
Citações na Scopus
4
Tipo de produção
article
Data de publicação
2023
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
SAGE PUBLICATIONS LTD
Autores
MATIAS, Isadora
DINIZ, Luan Pereira
ARAUJO, Ana Paula Bergamo
DAMICO, Isabella Vivarini
MOURA, Pamella de
CABRAL-MIRANDA, Felipe
DINIZ, Fabiola
PARMEGGIANI, Belisa
COELHO, Valeria de Mello
Citação
ASN NEURO, v.15, article ID 17590914231157900, 13p, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Aging is marked by complex and progressive physiological changes, including in the glutamatergic system, that lead to a decline of brain function. Increased content of senescent cells in the brain, such as glial cells, has been reported to impact cognition both in animal models and human tissue during normal aging and in the context of neurodegenerative disease. Changes in the glutamatergic synaptic activity rely on the glutamate-glutamine cycle, in which astrocytes handle glutamate taken up from synapses and provide glutamine for neurons, thus maintaining excitatory neurotransmission. However, the mechanisms of glutamate homeostasis in brain aging are still poorly understood. Herein, we showed that mouse senescent astrocytes in vitro undergo upregulation of GLT-1, GLAST, and glutamine synthetase (GS), along with the increased enzymatic activity of GS and [H-3]-D-aspartate uptake. Furthermore, we observed higher levels of GS and increased [H-3]-D-aspartate uptake in the hippocampus of aged mice, although the activity of GS was similar between young and old mice. Analysis of a previously available RNAseq dataset of mice at different ages revealed upregulation of GLAST and GS mRNA levels in hippocampal astrocytes during aging. Corroborating these rodent data, we showed an increased number of GS + cells, and GS and GLT-1 levels/intensity in the hippocampus of elderly humans. Our data suggest that aged astrocytes undergo molecular and functional changes that control glutamate-glutamine homeostasis upon brain aging.
Palavras-chave
astrocyte, glutamate-glutamine cycle, GLT-1, aging, hippocampus, senescence
URI
https://observatorio.fm.usp.br/handle/OPI/52838
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - LIM/22