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The mGluR5 positive allosteric modulator VU0409551 improves synaptic plasticity and memory of a mouse model of Huntington's disease.

التفاصيل البيبلوغرافية
العنوان: The mGluR5 positive allosteric modulator VU0409551 improves synaptic plasticity and memory of a mouse model of Huntington's disease.
المؤلفون: Doria JG; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., de Souza JM; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Silva FR; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Olmo IG; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Carvalho TG; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Alves-Silva J; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Ferreira-Vieira TH; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Santos JT; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Xavier CQS; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Silva NC; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Maciel EMA; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Conn PJ; Vanderbilt Center for Drug Discovery, Vanderbilt University, Nashville, TN, USA., Ribeiro FM; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
المصدر: Journal of neurochemistry [J Neurochem] 2018 Oct; Vol. 147 (2), pp. 222-239. Date of Electronic Publication: 2018 Sep 11.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley on behalf of the International Society for Neurochemistry Country of Publication: England NLM ID: 2985190R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1471-4159 (Electronic) Linking ISSN: 00223042 NLM ISO Abbreviation: J Neurochem Subsets: MEDLINE
أسماء مطبوعة: Publication: 2001- : Oxford, UK : Wiley on behalf of the International Society for Neurochemistry
Original Publication: New York : Raven Press
مواضيع طبية MeSH: Huntington Disease/*drug therapy , Huntington Disease/*psychology , Memory Disorders/*drug therapy , Memory Disorders/*psychology , Neuronal Plasticity/*drug effects , Oxazoles/*pharmacology , Pyridines/*pharmacology , Receptor, Metabotropic Glutamate 5/*drug effects , Synapses/*drug effects, Animals ; Conditioning, Classical/drug effects ; Dendritic Spines/drug effects ; Gene Expression Regulation/drug effects ; Huntington Disease/complications ; Memory Disorders/etiology ; Mice ; Mice, Inbred C57BL ; Motor Activity/drug effects ; Neuronal Plasticity/genetics ; Receptor, Metabotropic Glutamate 5/metabolism ; Recognition, Psychology/drug effects ; Signal Transduction/drug effects
مستخلص: Huntington's Disease (HD) is an autosomal-dominant neurodegenerative disorder, characterized by involuntary body movements, cognitive impairment, and psychiatric disorder. The metabotropic glutamate receptor 5 (mGluR5) plays an important role in HD and we have recently demonstrated that mGluR5-positive allosteric modulators (PAMs) can ameliorate pathology and the phenotypic signs of a mouse model of HD. In this study, we investigated the molecular mechanisms involved in mGluR5 PAMs effect on memory. Our results demonstrate that subchronic treatment with the mGluR5 PAM VU0409551 was effective in reversing the memory deficits exhibited by BACHD mice, a mouse model for HD. Moreover, VU0409551 treatment stabilized mGluR5 at the cellular plasma membrane of BACHD mice, increasing the expression of several genes important for synaptic plasticity, including c-Fos, brain-derived neurotrophic factor, Arc/Arg3.1, syntaxin 1A, and post-synaptic density-95. In addition, VU0409551 treatment also increased dendritic spine density and maturation and augmented the number of pre-synaptic sites. In conclusion, our results demonstrate that VU0409551 triggered the activation of cell signaling pathways important for synaptic plasticity, enhancing the level of dendritic spine maturation and rescuing BACHD memory impairment. OPEN PRACTICES: Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/.
(© 2018 International Society for Neurochemistry.)
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معلومات مُعتمدة: R01 MH062646 United States MH NIMH NIH HHS; R01 NS031373 United States NS NINDS NIH HHS; U54 HD083211 United States HD NICHD NIH HHS; U19 MH097056 United States MH NIMH NIH HHS; R37 NS031373 United States NS NINDS NIH HHS
فهرسة مساهمة: Keywords: Huntington's disease; VU0409551; memory; metabotropic glutamate receptor 5; synaptic plasticity
المشرفين على المادة: 0 (Grm5 protein, mouse)
0 (Oxazoles)
0 (Pyridines)
0 (Receptor, Metabotropic Glutamate 5)
0 (VU0409551)
تواريخ الأحداث: Date Created: 20180721 Date Completed: 20191002 Latest Revision: 20200306
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6317718
DOI: 10.1111/jnc.14555
PMID: 30028018
قاعدة البيانات: MEDLINE
الوصف
تدمد:1471-4159
DOI:10.1111/jnc.14555