2. Academic Validation
  3. Harmine exerts anxiolytic effects by regulating neuroinflammation and neuronal plasticity in the basolateral amygdala

Harmine exerts anxiolytic effects by regulating neuroinflammation and neuronal plasticity in the basolateral amygdala

  • Int Immunopharmacol. 2023 May 5;119:110208. doi: 10.1016/j.intimp.2023.110208.
Zhi-Heng Zheng 1,  Xing-Cheng Lin 2,  Ying Lu 1,  Shi-Rui Cao 3,  Xu-Kai Liu 4,  Dong Lin 1,  Fan-Hua Yang 5,  Yang-Bo Zhang 6,  Jiang-Long Tu 6,  Bing-Xing Pan 1,  Ping Hu 7,  Wen-Hua Zhang 8
Affiliations

Affiliations

  • 1 School of Life Science, Nanchang University, 330031 Nanchang, PR China; Laboratory of Fear and Anxiety Disorders, Institutes of Life Science, Nanchang University, Nanchang 330031, PR China.
  • 2 Institute of Translational Medicine, Nanchang University, Nanchang 330031, PR China.
  • 3 Laboratory of Fear and Anxiety Disorders, Institutes of Life Science, Nanchang University, Nanchang 330031, PR China; School of Basic Medical Sciences, Nanchang University, Nanchang 330031, PR China.
  • 4 Laboratory of Fear and Anxiety Disorders, Institutes of Life Science, Nanchang University, Nanchang 330031, PR China; School of Future Technology, Nanchang University, Nanchang 330031, PR China.
  • 5 Laboratory of Fear and Anxiety Disorders, Institutes of Life Science, Nanchang University, Nanchang 330031, PR China; Food Science and Technology, Nanchang University, Nanchang 330031, PR China.
  • 6 Department of Neurology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.
  • 7 Institute of Translational Medicine, Nanchang University, Nanchang 330031, PR China. Electronic address: canyhp@ncu.edu.cn.
  • 8 School of Life Science, Nanchang University, 330031 Nanchang, PR China; Laboratory of Fear and Anxiety Disorders, Institutes of Life Science, Nanchang University, Nanchang 330031, PR China; School of Basic Medical Sciences, Nanchang University, Nanchang 330031, PR China. Electronic address: whzhang@ncu.edu.cn.
PMID: 37150016 DOI: 10.1016/j.intimp.2023.110208
Abstract

Increasing evidence indicates that an altered immune system is closely linked to the pathophysiology of anxiety disorders, and inhibition of neuroinflammation may represent an effective therapeutic strategy to treat anxiety disorders. Harmine, a beta-carboline alkaloid in various medicinal Plants, has been widely reported to display anti-inflammatory and potentially anxiolytic effects. However, the exact underlying mechanisms are not fully understood. Our recent study has demonstrated that dysregulation of neuroplasticity in the basolateral amygdala (BLA) contributes to the pathological processes of inflammation-related anxiety. In this study, using a mouse model of anxiety challenged with Escherichia coli lipopolysaccharide (LPS), we found that harmine alleviated LPS-induced anxiety-like behaviors in mice. Mechanistically, harmine significantly prevented LPS-induced neuroinflammation by suppressing the expression of pro-inflammatory cytokines including IL-1β and TNF-α. Meanwhile, ex vivo whole-cell slice electrophysiology combined with optogenetics showed that LPS-induced increase of medial prefrontal cortex (mPFC)-driven excitatory but not inhibitory synaptic transmission onto BLA projection neurons, thereby alleviating LPS-induced shift of excitatory/inhibitory balance towards excitation. In addition, harmine attenuated the increased intrinsic neuronal excitability of BLA PNs by reducing the medium after-hyperpolarization. In conclusion, our findings provide new evidence that harmine may exert its anxiolytic effect by downregulating LPS-induced neuroinflammation and restoring the changes in neuronal plasticity in BLA PNs.

Keywords

Amygdala; Anxiety; Harmine; Neuroinflammation; Plasticity.

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