Microglia in the human infant brain and factors that affect expression

Area of Science:

• Neuroscience
• Immunology
• Developmental Biology

Background:

• Microglia are crucial immune cells in the brain, with their role in infant brain development not fully understood.
• Understanding microglial heterogeneity is key to deciphering infant neurological conditions.

Purpose of the Study:

• To map microglial populations across 34 regions of the human infant brain (1-11 months).
• To investigate the influence of developmental parameters and extrinsic factors (cigarette smoke, prone sleeping, URTI) on microglial expression.
• To compare microglial populations among sudden unexpected death in infancy (SUDI) subgroups: explained SUDI (eSUDI), SIDS I, and SIDS II.

Main Methods:

• Immunohistochemistry using Ionised calcium binding adaptor molecule-1 (Iba1) for microglial morphology and area.
• Assessment of microglial activation using cluster-of-differentiation factor 68 (CD68) and human leukocyte antigen-DP,DQ,DR (HLA).
• Analysis of regional microglial heterogeneity and correlations with developmental and extrinsic factors.

Main Results:

• Significant regional differences in microglial area and activation were observed across the infant brain.
• The hippocampus, basal ganglia, white matter, and cerebellar dentate nucleus showed larger microglial areas compared to the brainstem.
• Positive correlations between microglia and developmental parameters were found in the basal ganglia and cortex, while URTI and smoke exposure were linked to reduced microglial area.

Conclusions:

• Microglial distribution in the infant brain is heterogeneous and influenced by both intrinsic developmental and extrinsic factors.
• Specific microglial alterations were noted in SIDS II and SIDS I subgroups, suggesting their potential role in SUDI.
• The SIDS I group shows promise as a control for future research on infant central nervous system pathologies.