Microglia in the human infant brain and factors that affect expression

Abstract

The present study reports on the microglial populations present in 34 regions of the human infant brain (1–11 months), and whether developmental parameters or extrinsic factors such as cigarette smoke exposure, prone sleeping and an upper respiratory tract infection (URTI) influence their expression. Further, we compare microglia populations amongst three sudden unexpected death in infancy (SUDI) sub-groups: explained SUDI (eSUDI, n ​= ​7), sudden infant death syndrome (SIDS) I (n ​= ​8) and SIDS II (n ​= ​13). Ionised calcium binding adaptor molecule-1 (Iba1) was used to determine the morphology and area covered by microglia in a given brain region. Activation was explored using cluster-of-differentiation factor 68 (CD68) and human leukocyte antigen-DP,DQ,DR (HLA). We found regional heterogeneity in the area covered and activation status of microglia across the infant brain. The hippocampus, basal ganglia, white matter and dentate nucleus of the cerebellum showed larger areas of Iba1, while the brainstem had the smallest. Microglia in regions of the basal ganglia and cortex demonstrated positive correlations with infant developmental parameters, while in nuclei of the rostral medulla, negative correlations between microglia parameters were seen. URTI and cigarette smoke exposure were associated with a reduced microglial area in regions of the hippocampus and cortex (parietal and occipital), respectively. In the context of SIDS, a reduced microglial area was seen in SIDS II and fewer SIDS I infants demonstrated activated phenotypes in the hippocampus. Overall, we identify the distribution of microglia in the infant brain to be heterogenous, and influenced by intrinsic and extrinsic factors, and that the SIDS I group is a useful control group for future research into other infant CNS pathologies.

Immunostaining for NeuN Does Not Show all Mature and Healthy Neurons in the Human and Pig Brain: Focus on the Hippocampus

“…Other studies in our laboratory have identified cytoplasmic staining for active caspase-3, and α7 and β2 nicotinic acetylcholine receptor subunits, nuclear staining of fragmented DNA using TUNEL26 (see Figure, Supplemental Digital Content 4, http://links.lww.com/AIMM/A291), microglial markers37 and astrocytes [glial fibrillary acidic protein (GFAP)] in these same cases (see Figure, Supplemental Digital Content 4, http://links.lww.com/AIMM/A291). The lack of immunoreactivity for NeuN therefore appears specific to either the NeuN antibody, or loss of antigenicity of the target epitope.…”

The Science (or Nonscience) of Research Into Sudden Infant Death Syndrome (SIDS)

“…These include low-grade lung inflammation (35) and/or myocardial inflammation (35) and changes typical of haematogenous shock (36) and shock-like diaphragmatic muscular degeneration (37,38). Neuropathological features that could reflect shock include neuronal apoptosis (39) and microglial activation (40). Microbiological investigation reveals detection of bacterial toxins in SIDS tissues (41,42), isolation of bacterial pathogens (e.g., Staphylococcus aureus and Escherichia coli) from normally sterile sites (43,44), and despite these clues, infection and sepsis have not been widely examined in relation to most aspects of SIDS research and despite the findings of those proposing the Infection Model of SIDS (25-32, 35, 41-49).…”

Microglia in Circumventricular Organs: The Pineal Gland Example

“…However, CVO microglia do resemble the activated microglial forms found in the rest of the CNS under unhealthy and stimulating conditions ( Leyh et al, 2021 ). In the CVOs as compared to other brain regions, to the best of my knowledge, a fine characterization of microglia morphotypes has not been done yet for both humans and non-human primates ( Ambrose et al, 2020 ; Barger et al, 2019 ; Cooper et al, 2018 ; Morgan et al, 2014 ; Rezaie and Male, 1999 ; Salamanca et al, 2019 ).…”