دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: mGluR5 ablation leads to age-related synaptic plasticity impairments and does not improve Huntington's disease phenotype.
المؤلفون: 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.
المصدر: Scientific reports [Sci Rep] 2022 May 28; Vol. 12 (1), pp. 8982. Date of Electronic Publication: 2022 May 28.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Huntington Disease*/genetics , Huntington Disease*/metabolism , Neurodegenerative Diseases*/metabolism, Animals ; Brain/metabolism ; Memory Disorders/genetics ; Memory Disorders/metabolism ; Mice ; Neuronal Plasticity ; Phenotype
مستخلص: 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).)
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تواريخ الأحداث: Date Created: 20220601 Date Completed: 20220603 Latest Revision: 20220726
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9148310
DOI: 10.1038/s41598-022-13029-z
PMID: 35643779
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-022-13029-z