2. Academic Validation
  3. Berberine ameliorates depression-like behaviors in mice via inhibiting NLRP3 inflammasome-mediated neuroinflammation and preventing neuroplasticity disruption

Berberine ameliorates depression-like behaviors in mice via inhibiting NLRP3 inflammasome-mediated neuroinflammation and preventing neuroplasticity disruption

  • J Neuroinflammation. 2023 Mar 1;20(1):54. doi: 10.1186/s12974-023-02744-7.
Zongshi Qin # 1 2,  Dong-Dong Shi # 3,  Wenqi Li 2,  Dan Cheng 2,  Ying-Dan Zhang 3,  Sen Zhang 3,  Bun Tsoi 4,  Jia Zhao 2,  Zhen Wang 5,  Zhang-Jin Zhang 6
Affiliations

Affiliations

  • 1 Peking University Clinical Research Institute, Peking University, Beijing, China.
  • 2 School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
  • 3 Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong SAR, China.
  • 5 Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 6 School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. [email protected].
  • # Contributed equally.
PMID: 36859349 DOI: 10.1186/s12974-023-02744-7
Abstract

Objectives: Neuroinflammation has been suggested that affects the processing of depression. There is renewed interest in berberine owing to its anti-inflammatory effects. Herein, we investigated whether berberine attenuate depressive-like behaviors via inhibiting NLRP3 inflammasome activation in mice model of depression.

Methods: Adult male C57BL/6N mice were administrated corticosterone (CORT, 20 mg/kg/day) for 35 days. Two doses (100 mg/kg/day and 200 mg/kg/day) of berberine were orally administrated from day 7 until day 35. Behavioral tests were performed to measure the depression-like behaviors alterations. Differentially expressed gene analysis was performed for RNA-sequencing data in the prefrontal cortex. NLRP3 inflammasome was measured by quantitative reverse transcription polymerase chain reaction, western blotting, and immunofluorescence labeling. The neuroplasticity and synaptic function were measured by immunofluorescence labeling, Golgi-Cox staining, transmission electron microscope, and whole-cell patch-clamp recordings.

Results: The results of behavioral tests demonstrated that berberine attenuated the depression-like behaviors induced by CORT. RNA-sequencing identified that NLRP3 was markedly upregulated after long-term CORT exposure. Berberine reversed the concentrations of peripheral and brain cytokines, NLRP3 inflammasome elicited by CORT in the prefrontal cortex and hippocampus were decreased by berberine. In addition, the lower frequency of neuronal excitation as well as the dendritic spine reduction were reversed by berberine treatment. Together, berberine increases hippocampal adult neurogenesis and synaptic plasticity induced by CORT.

Conclusion: The anti-depressants effects of berberine were accompanied by reduced the neuroinflammatory response via inhibiting the activation of NLRP3 inflammasome and rescued the neuronal deterioration via suppression of impairments in synaptic plasticity and neurogenesis.

Keywords

Berberine; Depression; NLRP3 inflammasome; Neuroinflammation; Synaptic plasticity.

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