دورية أكاديمية
أعرض في EDS

Positive modulation of mGluR5 attenuates seizures and reduces TNF-α + macrophages and microglia in the brain in a murine model of virus-induced temporal lobe epilepsy.

التفاصيل البيبلوغرافية
العنوان: Positive modulation of mGluR5 attenuates seizures and reduces TNF-α + macrophages and microglia in the brain in a murine model of virus-induced temporal lobe epilepsy.
المؤلفون: Hanak TJ; Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT 84112, USA; Interdepartmental Program in Neuroscience, University of Utah, 20 South 2030 East, Salt Lake City, UT 84112, USA., Libbey JE; Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT 84112, USA., Doty DJ; Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT 84112, USA., Sim JT; Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT 84112, USA., DePaula-Silva AB; Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT 84112, USA., Fujinami RS; Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT 84112, USA. Electronic address: Robert.Fujinami@hsc.utah.edu.
المصدر: Experimental neurology [Exp Neurol] 2019 Jan; Vol. 311, pp. 194-204. Date of Electronic Publication: 2018 Oct 11.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Academic Press Country of Publication: United States NLM ID: 0370712 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2430 (Electronic) Linking ISSN: 00144886 NLM ISO Abbreviation: Exp Neurol Subsets: MEDLINE
أسماء مطبوعة: Publication: Orlando Fl : Academic Press
Original Publication: New York.
مواضيع طبية MeSH: Theilovirus*, Epilepsy, Temporal Lobe/*metabolism , Macrophages/*metabolism , Microglia/*metabolism , Receptor, Metabotropic Glutamate 5/*metabolism , Tumor Necrosis Factor-alpha/*metabolism, Animals ; Brain/metabolism ; Brain/virology ; Epilepsy, Temporal Lobe/prevention & control ; Epilepsy, Temporal Lobe/virology ; Male ; Mice ; Mice, Inbred C57BL ; Seizures/metabolism ; Seizures/prevention & control ; Seizures/virology ; Tumor Necrosis Factor-alpha/antagonists & inhibitors
مستخلص: Viral encephalitis markedly increases the risk for the development of epilepsy. The Theiler's murine encephalomyelitis virus (TMEV)-induced model of seizures/epilepsy is a murine model of both viral-induced seizures/epilepsy and human Temporal Lobe Epilepsy. The inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α have been shown to play a role in seizure development in the TMEV-induced model of seizures/epilepsy, and infiltrating macrophages along with microglia have been shown to be major producers of these cytokines. The metabotropic glutamate receptor 5 (mGluR5) is a G-protein coupled receptor that has been shown to reduce IL-6 and TNF-α and to provide neuroprotection in other disease models. Therefore, we hypothesized that stimulation of mGluR5 would not only reduce seizures but attenuate IL-6 and TNF-α production in microglia and macrophages in the TMEV model. We found that pharmacological stimulation of mGluR5 with the selective positive allosteric modulator VU0360172 not only reduced acute seizure outcomes, but also reduced the percent of microglia and macrophages producing TNF-α 3 days post infection. Furthermore, treatment with VU0360172 did not alter the level of viral antigen, compared to controls, showing that this treatment does not compromise viral clearance. These results establish that mGluR5 may represent a therapeutic target in the TMEV-induced model of seizures/epilepsy.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: R01 NS065714 United States NS NINDS NIH HHS; S10 RR024761 United States RR NCRR NIH HHS; T32 AI055434 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: Epilepsy; Metabotropic glutamate receptor 5; Picornavirus; Seizures; Temporal lobe epilepsy; Theiler's murine encephalomyelitis virus; Tumor necrosis factor α; VU0360172; Viral encephalitis
المشرفين على المادة: 0 (Grm5 protein, mouse)
0 (Receptor, Metabotropic Glutamate 5)
0 (Tumor Necrosis Factor-alpha)
تواريخ الأحداث: Date Created: 20181015 Date Completed: 20190410 Latest Revision: 20200102
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6263825
DOI: 10.1016/j.expneurol.2018.10.006
PMID: 30316834
قاعدة البيانات: MEDLINE
الوصف
تدمد:1090-2430
DOI:10.1016/j.expneurol.2018.10.006