Bullatine A has an antidepressant effect in chronic social defeat stress mice; Implication of microglial inflammasome

  • Brain Res Bull. 2023 Apr:195:130-140. doi: 10.1016/j.brainresbull.2023.02.015.
Jia-Rui Zhang  1 ,  Shu-Yuan Yin  1 ,  Zu-Qi Shen  1 ,  Bing Li  2 ,  Yu-Qiu Zhang  3 ,  Jin Yu  4
Affiliations
  • 1. Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • 2. Center Laboratories, Jinshan Hospital of Fudan University, Shanghai 201508, China.
  • 3. Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • 4. Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Fudan University, Shanghai 200433, China. Electronic address: [email protected].
PMID: 36828203 DOI: 10.1016/j.brainresbull.2023.02.015
Abstract

Inflammatory microglia and P2X7R are involved in the development of stress-induced depression. Endoplasmic reticulum (ER) stress and mitochondrial damage play an important role in depression and microglial activation. Bullatine A (BLA) has anti-inflammatory and anti-rheumatic effects, and can be used as a P2X7R antagonist. We found that Bullatine A can effectively inhibit the calcium overload of mitochondria and the increase of ER and mitochondrial colocalization caused by eATP (extracellular ATP) in BV2-cells. Bullatine A can also inhibit the activation of PERK-elF-2α unfolded protein response (UPR), lysosome production and the increase of NLRP3 inflammasome protein expression in BV2-cells Both intragastric administration and intra-hippocampal microinjection of Bullatine A can significantly improve the despair behavior but not anhedonia of Chronic chronic social defeat stress (CSDS) mice. Bullatine A may have a beneficial therapeutic effect in treating diseases related to stress stimulation, such as depression.

Keywords
Antidepressant; Bullatine A; Endoplasmic reticulum; MAMs; Mitochondrial.
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