Betaine eliminates CFA-induced depressive-like behaviour in mice may be through inhibition of microglia and astrocyte activation and polarization

Yue Liang; Ling Chen; Yanmei Huang; Lihua Xie; Xueqin Liu; Wenyan Zhou; Wenyu Cao; Zuyao Chen; Xiaolin Zhong

doi:10.1016/j.brainresbull.2023.110863

Betaine eliminates CFA-induced depressive-like behaviour in mice may be through inhibition of microglia and astrocyte activation and polarization

Brain Res Bull. 2024 Jan:206:110863. doi: 10.1016/j.brainresbull.2023.110863. Epub 2023 Dec 23.

Authors

Yue Liang¹, Ling Chen², Yanmei Huang³, Lihua Xie³, Xueqin Liu², Wenyan Zhou², Wenyu Cao⁴, Zuyao Chen⁵, Xiaolin Zhong⁶

Affiliations

¹ The First Affiliated Hospital, Department of Endocrinology and Metabolism, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China; The First Affiliated Hospital, Department of Laboratory Medicine, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China.
² The First Affiliated Hospital, Department of Endocrinology and Metabolism, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China.
³ The First Affiliated Hospital, Department of Laboratory Medicine, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China.
⁴ Department of Human Anatomy, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China.
⁵ The First Affiliated Hospital, Department of Otorhinolaryngology, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China. Electronic address: chenzuyao@usc.edu.cn.
⁶ The First Affiliated Hospital, Department of Endocrinology and Metabolism, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China. Electronic address: zhxl520@usc.edu.cn.

PMID: 38145759
DOI: 10.1016/j.brainresbull.2023.110863

Abstract

Chronic pain can induce not only nociceptive but also depressive emotions. A previous study demonstrated that betaine, a commonly used nutrient supplement, has an anti-nociceptive effect, but whether betaine can alleviate chronic pain-induced depressive emotion is elusive. Our current study found that betaine administration significantly eliminated complete Freund's adjuvant (CFA)-induced pain-related depressive-like behaviour. Mechanistically, betaine treatment inhibited microglia and astrocyte activation. Furthermore, betaine significantly promoted the transition of microglia from the M1 to the M2 phenotype, as well as the transition of astrocytes from the A1 to the A2 phenotype. Additionally, the release of pro-inflammatory factors such as IL-18, IL-1β and IL-6 and anti-inflammatory factors such as IL-10 in the hippocampus induced by CFA were also reversed by betaine administration. Overall, betaine has therapeutic effects on pain-related depressive-like phenotypes caused by CFA, possibly through altering the polarization of microglia and astrocytes to reduce neuroinflammation.

Keywords: Astrocyte polarization; Betaine; Microglia polarization; Pain-related depressive-like behaviour.

MeSH terms

Animals
Astrocytes
Betaine / adverse effects
Chronic Pain*
Freund's Adjuvant / toxicity
Inflammation / genetics
Mice
Microglia*

Substances

Betaine
Freund's Adjuvant