Human umbilical cord blood mesenchymal stem cells mediate microglia activation and improve anxiety-like behavior in MIA-induced offspring of schizophrenic rats

Xiangzheng Cui; Tengfei Chen; Yongjiang Xue; Zhongqi Wu; Pengyue Yan; Yongfeng Yang; Xi Su; Minglong Shao; Meng Song; Yi Chen; Ning Kang; Qing Liu; Luwen Zhang; Luxian Lv; Suqin Guo; Wenqiang Li

doi:10.1016/j.pnpbp.2024.111010

Human umbilical cord blood mesenchymal stem cells mediate microglia activation and improve anxiety-like behavior in MIA-induced offspring of schizophrenic rats

Prog Neuropsychopharmacol Biol Psychiatry. 2024 Apr 18:133:111010. doi: 10.1016/j.pnpbp.2024.111010. Online ahead of print.

Authors

Xiangzheng Cui¹, Tengfei Chen², Yongjiang Xue¹, Zhongqi Wu³, Pengyue Yan¹, Yongfeng Yang², Xi Su², Minglong Shao², Meng Song², Yi Chen², Ning Kang², Qing Liu², Luwen Zhang², Luxian Lv², Suqin Guo², Wenqiang Li⁴

Affiliations

¹ Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453002, China; Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang 453002, China.
² Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453002, China; Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang 453002, China; International Joint Research Laboratory for Psychiatry and Neuroscience of Henan, Xinxiang 453002, China.
³ Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453002, China; Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang 453002, China; Xinxiang Siwei Brain Science Research Institute, Xinxiang 453002, China.
⁴ Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453002, China; Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang 453002, China; International Joint Research Laboratory for Psychiatry and Neuroscience of Henan, Xinxiang 453002, China; Henan Collaborative Innovation Center of Prevention and Treatment of Mental Disorder, Xinxiang 453002, China. Electronic address: lwq781603@163.com.

PMID: 38642731
DOI: 10.1016/j.pnpbp.2024.111010

Abstract

Current treatments for schizophrenia (SCZ) remain largely ineffective in one-third of patients. Recent studies using stem cell therapy show a close relationship between stem cell immunomodulatory function and neuroinflammation in SCZ. To better investigate the efficacy of stem cell therapy for SCZ, human umbilical cord blood mesenchymal stem cells (hUC-MSC) with powerful immunomodulatory effects were administered to rats via the tail vein (once a week for 5 consecutive weeks starting from the weaning period) using a maternal immune activation (MIA) rodent model. Open field, PPI, Western blotting, Q-PCR, and immunofluorescence were used to assess the biological effects of repeated tail vein injections of hUC-MSC in offspring rats following the MIA model of SCZ. The results indicated that offspring of MIA rats exhibited schizophrenia-like (SCZ-like) anxiety behavior, with observed microglial activation triggering neuroinflammation. Furthermore, levels of IBA1, HMGB1, and PSD95 were significantly up-regulated, while SYP was significantly down-regulated. It is suggested that hUCB-MSCs may act through HMGB1, Iba1, PSD95, and related pathway molecules to alleviate neuroinflammation and repair synaptic damage by regulating the activity state of microglia. Consequently, this could improve the abnormal behavior observed in MIA offspring rats.

Keywords: Human umbilical cord blood mesenchymal stem cells; Microglia; Neuroinflammation; Schizophrenia.