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Metabotropic glutamate receptor 5 ablation accelerates age-related neurodegeneration and neuroinflammation.
Carvalho, Toniana G; Alves-Silva, Juliana; de Souza, Jessica M; Real, Ana L C V; Doria, Juliana G; Vieira, Erica L M; Gomes, Giovanni F; de Oliveira, Antonio C; Miranda, Aline S; Ribeiro, Fabiola M.
Afiliación
  • Carvalho TG; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
  • Alves-Silva J; Department of Morphology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
  • de Souza JM; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
  • Real ALCV; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
  • Doria JG; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
  • Vieira ELM; Interdisciplinary Laboratory of Medical Investigation, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 30130-100, Brazil.
  • Gomes GF; Department of Pharmacology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
  • de Oliveira AC; Department of Pharmacology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
  • Miranda AS; Department of Morphology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
  • Ribeiro FM; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil. Electronic address: fmribeiro@icb.ufmg.br.
Neurochem Int ; 126: 218-228, 2019 06.
Article en En | MEDLINE | ID: mdl-30930274
The growing elderly population world widely prompts the need for studies regarding aged brain and its susceptibility to neurodegenerative diseases. It has been shown that aged brain exhibits several alterations, including neuroinflammation, which prone this organ to neurodegenerative processes. Metabotropic glutamate receptor 5 (mGlu5 receptor) has a role in neuronal cell loss and inflammation. Although the relevance of mGlu5 receptor in different diseases has been investigated, its involvement in normal brain aging remains unclear. In the present study, we used the mGlu5 receptor knockout (mGluR5-/-) mice, a model of Huntington's Disease (BACHD), and the double mutant mice (mGluR5-/-/BACHD), at the ages of 2, 6 and 12 months, to investigate whether mGlu5 receptor has a role in brain aging. We demonstrated that mGluR5-/- mice exhibit diminished number of neurons at 12 months of age in the cortex and striatum, similarly to what was observed in the case of BACHD and mGluR5-/-/BACHD mice. In addition, ablation of mGlu5 receptor increased the number of astrocytes and microglia in BACHD and wild type (WT) mice in an age-dependent manner in the cortical region, but not in the striatum. Interestingly, 12-month-old mGluR5-/- mice induced microglia activation, evidenced by increased CD68 expression and diminished number of microglia ramifications in skeleton analyses. Importantly, the presence of mutant huntingtin and the absence of mGlu5 receptor promoted decreased levels of fractalkine expression in aged mice, which could account for the decreased levels of microglia activation in these mice. Together, our data provide evidence that mGlu5 receptor plays a role in brain aging by modulating different cell types in the central nervous system (CNS).
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Envejecimiento / Mediadores de Inflamación / Enfermedades Neurodegenerativas / Receptor del Glutamato Metabotropico 5 Límite: Animals Idioma: En Revista: Neurochem Int Año: 2019 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Envejecimiento / Mediadores de Inflamación / Enfermedades Neurodegenerativas / Receptor del Glutamato Metabotropico 5 Límite: Animals Idioma: En Revista: Neurochem Int Año: 2019 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido