Possible involvement of microglial P2RY12 and peripheral IL-10 in postpartum depression

Hui-Ju Kim; Min-Jung You; Soyoung Sung; Chan Rim; Min-Soo Kwon

doi:10.3389/fncel.2023.1162966

Possible involvement of microglial P2RY12 and peripheral IL-10 in postpartum depression

Front Cell Neurosci. 2023 Jun 15:17:1162966. doi: 10.3389/fncel.2023.1162966. eCollection 2023.

Authors

Hui-Ju Kim¹, Min-Jung You¹, Soyoung Sung¹, Chan Rim¹, Min-Soo Kwon¹

Affiliation

¹ Department of Pharmacology, Research Institute for Basic Medical Science, School of Medicine, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea.

Abstract

Postpartum depression (PPD) is another type of depression, including emotional fluctuation, fatigue, and anxiety. Based on the specific event like giving birth, it can be speculated that PPD might have its specific mechanism. Here, we confirmed that dexamethasone (DEX) administration during pregnancy (gestational days 16-18) induced depressive- and anxiety-like behaviors in dam (DEX-dam) after weaning period (3 weeks). DEX-dam showed anxiety-like behaviors in open-field test (OFT) and light-dark test (LD). In addition, DEX-dam exhibited depressive-like behaviors with the increased immobility time in forced swimming test (TST). Molecular analysis confirmed that microglia, rather than neurons, astrocytes, and oligodendrocytes, are involved in anxiety-/depressive-like behaviors. Notably, P2ry12, homeostatic gene, and purinoceptor, along with hyper-ramified form, were reduced in the hippocampus of DEX-dam. In addition, we found that IL-10 mRNA was reduced in lymph nodes without alteration of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6. Interestingly, anxiety-/depressive-like behaviors of DEX-dam were restored with the normalization of P2ry12 and IL-10 after 10 weeks postpartum without antidepressants. Our results propose that stress hormone elevation during pregnancy might be associated with PPD via microglial P2RY12 and peripheral IL-10.

Keywords: IL-10; P2RY12; glial cells; microglia; postpartum depression.

Grants and funding

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MIST) (2019M3C7A1032561, 2021M3E5D9025027, and 2021R1I1A1A01059611).