Postpartum Brain Reveals Repopulating Process and Long-Lasting Proteomic Changes of Microglia

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• The maternal brain undergoes significant neuroplastic changes during pregnancy and postpartum.
• The specific roles and cellular dynamics of microglia in the postpartum brain remain largely unknown.

Purpose of the Study:

• To investigate microglial dynamics, including number, origin, and proteomic profile, in the peripartum and postpartum mouse brain.
• To understand whether postpartum microglial replenishment occurs via resident proliferation or peripheral monocyte infiltration.

Main Methods:

• Assessed microglial sources (resident proliferation vs. peripheral infiltration).
• Isolated CD11b+ microglia from postpartum brain tissue using MACS for proteomic profiling via LC-MS/MS.
• Conducted subregional proteomic analysis, focusing on the hippocampus.

Main Results:

• Hippocampal microglia numbers decreased after parturition, followed by repopulation mainly through resident proliferation.
• Microglia from 50 days postpartum (PP50) displayed a reduced aging-associated inflammatory profile compared to controls.
• Proteomic analysis revealed significant, region-specific changes in the hippocampus, with PP50 microglia profiles distinct from neurodegenerative microglia phenotypes (MGnD, DAM, LDAM).

Conclusions:

• Parturition induces long-lasting, region-specific alterations in the maternal microglial proteome.
• Postpartum microglial repopulation is primarily driven by resident proliferation.
• The maternal brain's microglia exhibit a unique, less inflammatory profile postpartum, differing from neurodegenerative states.