mGluR5 ablation leads to age-related synaptic plasticity impairments and does not improve Huntington's disease phenotype.

Autor: de Souza JM; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Ave. Antonio Carlos 6627, Belo Horizonte, MG, CEP: 31270-901, Brazil., Ferreira-Vieira TH; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Ave. Antonio Carlos 6627, Belo Horizonte, MG, CEP: 31270-901, Brazil., Maciel EMA; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Ave. Antonio Carlos 6627, Belo Horizonte, MG, CEP: 31270-901, Brazil., Silva NC; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Ave. Antonio Carlos 6627, Belo Horizonte, MG, CEP: 31270-901, Brazil., Lima IBQ; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Ave. Antonio Carlos 6627, Belo Horizonte, MG, CEP: 31270-901, Brazil., Doria JG; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Ave. Antonio Carlos 6627, Belo Horizonte, MG, CEP: 31270-901, Brazil., Olmo IG; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Ave. Antonio Carlos 6627, Belo Horizonte, MG, CEP: 31270-901, Brazil., Ribeiro FM; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Ave. Antonio Carlos 6627, Belo Horizonte, MG, CEP: 31270-901, Brazil. fmribeiro@icb.ufmg.br.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 May 28; Vol. 12 (1), pp. 8982. Date of Electronic Publication: 2022 May 28.
DOI: 10.1038/s41598-022-13029-z
Abstrakt: Glutamate receptors, including mGluR5, are involved in learning and memory impairments triggered by aging and neurological diseases. However, each condition involves distinct molecular mechanisms. It is still unclear whether the mGluR5 cell signaling pathways involved in normal brain aging differ from those altered due to neurodegenerative disorders. Here, we employed wild type (WT), mGluR5 -/- , BACHD, which is a mouse model of Huntington's Disease (HD), and mGluR5 -/- /BACHD mice, at the ages of 2, 6 and 12 months, to distinguish the mGluR5-dependent cell signaling pathways involved in aging and neurodegenerative diseases. We demonstrated that the memory impairment exhibited by mGluR5 -/- mice is accompanied by massive neuronal loss and decreased dendritic spine density in the hippocampus, similarly to BACHD and BACHD/mGluR5 -/- mice. Moreover, mGluR5 ablation worsens some of the HD-related alterations. We also show that mGluR5 -/- and BACHD/mGluR5 -/- mice have decreased levels of PSD95, BDNF, and Arc/Arg3.1, whereas BACHD mice are mostly spared. PSD95 expression was affected exclusively by mGluR5 ablation in the aging context, making it a potential target to treat age-related alterations. Taken together, we reaffirm the relevance of mGluR5 for memory and distinguish the mGluR5 cell signaling pathways involved in normal brain aging from those implicated in HD.
(© 2022. The Author(s).)
Databáze: MEDLINE
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