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Dimethyl fumarate ameliorates chronic stress-induced anxiety-like behaviors by decreasing neuroinflammation and neuronal activity in the amygdala.

التفاصيل البيبلوغرافية
العنوان: Dimethyl fumarate ameliorates chronic stress-induced anxiety-like behaviors by decreasing neuroinflammation and neuronal activity in the amygdala.
المؤلفون: Wang CY; School of Life Science, Nanchang University, Nanchang 330031, China; Laboratory of Fear and Anxiety Disorders, Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China., Jiang SY; Laboratory of Fear and Anxiety Disorders, Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China., Liao SM; Laboratory of Fear and Anxiety Disorders, Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China., Tian-Liu; School of Life Science, Nanchang University, Nanchang 330031, China; Laboratory of Fear and Anxiety Disorders, Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China., Wu QS; Laboratory of Fear and Anxiety Disorders, Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China., Pan HQ; Laboratory of Fear and Anxiety Disorders, Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China., Wei-Nie; Laboratory of Fear and Anxiety Disorders, Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China., Zhang WH; School of Life Science, Nanchang University, Nanchang 330031, China; Laboratory of Fear and Anxiety Disorders, Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China. Electronic address: whzhang@ncu.edu.cn., Pan BX; Laboratory of Fear and Anxiety Disorders, Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China. Electronic address: panbingxing@ncu.edu.cn., Liu WZ; Laboratory of Fear and Anxiety Disorders, Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China; Department of Pathology, The 1(st) Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China. Electronic address: liuwz@ncu.edu.cn.
المصدر: International immunopharmacology [Int Immunopharmacol] 2024 Aug 20; Vol. 137, pp. 112414. Date of Electronic Publication: 2024 Jun 18.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam ; New York : Elsevier Science, c2001-
مواضيع طبية MeSH: Dimethyl Fumarate*/pharmacology , Dimethyl Fumarate*/therapeutic use , Stress, Psychological*/drug therapy , Stress, Psychological*/immunology , Anxiety*/drug therapy , Neurons*/drug effects , Mice, Inbred C57BL* , NLR Family, Pyrin Domain-Containing 3 Protein*/metabolism, Animals ; Male ; Mice ; Amygdala/drug effects ; Amygdala/metabolism ; Neuroinflammatory Diseases/drug therapy ; Neuroinflammatory Diseases/immunology ; Disease Models, Animal ; Interleukin-1beta/metabolism ; Microglia/drug effects ; Behavior, Animal/drug effects ; Caspase 1/metabolism ; Anti-Inflammatory Agents/therapeutic use ; Anti-Inflammatory Agents/pharmacology ; Signal Transduction/drug effects ; Social Defeat
مستخلص: Background: Chronic stress-induced neuroinflammation plays a pivotal role in the development and exacerbation of mental disorders, such as anxiety and depression. Dimethyl Fumarate (DMF), an effective therapeutic agent approved for the treatment of multiple sclerosis, has been widely reported to display anti-inflammatory and anti-oxidative effects. However, the impact of DMF on chronic stress-induced anxiety disorders and the exact underlying mechanisms remain largely unknown.
Methods: We established a mouse model of chronic social defeat stress (CSDS). DMF was administered orally 1 h before daily stress session for 10 days in CSDS + DMF group. qRT-PCR and western blotting were used to analyze mRNA and protein expression of NLRP3, Caspase-1 and IL-1β. Immunofluorescence staining was carried out to detect the expression of Iba 1 and c-fos positive cells as well as morphological change of Iba 1 + microglia. Whole-cell patch-clamp recording was applied to evaluate synaptic transmission and intrinsic excitability of neurons.
Results: DMF treatment significantly alleviated CSDS-induced anxiety-like behaviors in mice. Mechanistically, DMF treatment prevented CSDS-induced neuroinflammation by inhibiting the activation of microglia and NLRP3/Caspase-1/IL-1β signaling pathway in basolateral amygdala (BLA), a brain region important for emotional processing. Furthermore, DMF treatment effectively reversed the CSDS-caused disruption of excitatory and inhibitory synaptic transmission balance, as well as the increased intrinsic excitability of BLA neurons.
Conclusions: Our findings provide new evidence that DMF may exert anxiolytic effect by preventing CSDS-induced activation of NLRP3/Caspase-1/IL-1β signaling pathway and alleviating hyperactivity of BLA neurons.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Amygdala; Anxiety disorders; Chronic stress; DMF; Neuroinflammation; Neuronal activity
المشرفين على المادة: FO2303MNI2 (Dimethyl Fumarate)
0 (NLR Family, Pyrin Domain-Containing 3 Protein)
0 (Interleukin-1beta)
EC 3.4.22.36 (Caspase 1)
0 (Anti-Inflammatory Agents)
0 (Nlrp3 protein, mouse)
تواريخ الأحداث: Date Created: 20240619 Date Completed: 20240710 Latest Revision: 20240710
رمز التحديث: 20240710
DOI: 10.1016/j.intimp.2024.112414
PMID: 38897132
قاعدة البيانات: MEDLINE
الوصف
تدمد:1878-1705
DOI:10.1016/j.intimp.2024.112414