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

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

  • Int Immunopharmacol. 2024 Jun 18:137:112414. doi: 10.1016/j.intimp.2024.112414.
Chun-Yan Wang 1,  Si-Ying Jiang 2,  Shuang-Mei Liao 2,  Tian-Liu 1,  Qi-Sheng Wu 2,  Han-Qing Pan 2,  Wei-Nie 2,  Wen-Hua Zhang 3,  Bing-Xing Pan 4,  Wei-Zhu Liu 5
Affiliations

Affiliations

  • 1 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.
  • 2 Laboratory of Fear and Anxiety Disorders, Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China.
  • 3 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.
  • 4 Laboratory of Fear and Anxiety Disorders, Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China. Electronic address: panbingxing@ncu.edu.cn.
  • 5 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.
PMID: 38897132 DOI: 10.1016/j.intimp.2024.112414
Abstract

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.

Keywords

Amygdala; Anxiety disorders; Chronic stress; DMF; Neuroinflammation; Neuronal activity.

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