hUC-MSCs ameliorated CUMS-induced depression by modulating complement C3 signaling-mediated microglial polarization during astrocyte-microglia crosstalk.

Brain Research Bulletin
Jing LiBaoyong Yan

Abstract

Major depressive disorder (MDD) has been shown to be related to immune inflammation and the complement system. Previous studies have suggested that human umbilical cord mesenchymal stem cells (hUC-MSCs) play an important role in inflammatory diseases. hUC-MSCs were administered into chronic unpredictable mild stress model (CUMS) mice through the tail vein once a week for 4 weeks. After the administration of hUC-MSCs, the depression-like and anxiety-like phenotypes, neuronal histopathology, synaptic-related protein expression and inflammatory index of the mice were assessed. Microglial M1/M2 polarization and the expression of C3a in astrocytes and C3aR in microglia was detected by immunofluorescence co-localization. Then, CUMS mice were injected with a C3aR antagonist, and the expression of C3a and C3aR and microglial polarization were observed. Based on the sucrose preference and tail suspension tests, hUC-MSCs ameliorated the depression-like behaviors of CUMS mice. Additionally, the anxiety-like behaviors of CUMS mice in the open-field and plus-maze tests were improved after the administration of hUC-MSCs. hUC-MSCs altered microglia polarization by alleviating complement C3a-C3aR signaling activation, which decreased pro-infla...Continue Reading

Related Concepts

Related Feeds

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.