Clinical neuropathology practice guide 5-2013: markers of neuronal maturation

Abstract

This review surveys immunocytochemical and histochemical markers of neuronal lineage for application to tissue sections of fetal and neonatal brain. They determine maturation of individual nerve cells as the tissue progresses to mature architecture. From a developmental perspective, neuronal markers are all about timing. These diverse cellular labels may be classified in two ways: 1) time of onset of expression (early; intermediate; late); 2) labeling of subcellular structures or metabolic functions (nucleoproteins; synaptic vesicle proteins; enolases; cytoskeletal elements; calcium-binding; nucleic acids; mitochondria). Apart from these positive markers of maturation, other negative markers are expressed in primitive neuroepithelial cells and early stages of neuroblast maturation, but no longer are demonstrated after initial stages of maturation. These examinations are relevant for studies of normal neuroembryology at the cellular level. In fetal and perinatal neuropathology they provide control criteria for application to malformations of the brain, inborn metabolic disorders and acquired fetal insults in which neuroblastic maturation may be altered. Disorders, in which cells differentiate abnormally, as in tuberous sclerosis and hemimegalencephaly, pose another yet aspect of mixed cellular lineage. The measurement in living patients, especially neonates, of serum and CSF levels of enolases, chromogranins and S-100 proteins as biomarkers of brain damage may potentially be correlated with their corresponding tissue markers at autopsy in infants who do not survive. The neuropathological markers here described can be performed in ordinary hospital laboratories, not just research facilities, and offer another dimension of diagnostic precision in interpreting abnormally developed fetal and postnatal brains.

Immunocytochemical markers of neuronal maturation in human diagnostic neuropathology

“…(10) Traditional histochemical stains of frozen sections are still routinely performed for muscle biopsies but only occasionally for human brain tissue, except for frozen sections stained with H&E for intraoperative provisional diagnosis. Fetal brain and malformations In immature brain and in developmental malformations, ICC remains the principal technique for examination and for the determination of maturation by neuropathologists (Sarnat 2013). Nevertheless, the genetic basis underlying many malformations is known, particularly for neuroblast migratory disorders such as the lissencephalies and periventricular and subcortical laminar heterotopia and hence genetic studies can be performed but even some of these are now studied by ICC.…”

Functional properties of different collagen scaffolds to create a biomimetic niche for neurally committed human induced pluripotent stem cells (iPSC)

“…As shown in this study, the cells expressing neuronal markers expand protrusions along the pore edges and their interconnecting lamellas. It was earlier noted [31,32] that the pores in Col-CS sponges are ellipsoidal in shape and are oriented parallel to the surface within the sponge, what may influence cell distribution with a tendency to form cell monolayers as compared to aggregates found on Col-DAC. This may explain the preferential appearance of the differentiated cells forming the monolayers on the Col-CS as compared to cell aggregates with defined centres of proliferation on Col-DAC, as revealed by immunofluorescence in Fig.…”

“…3 and 5), which binds to the nuclear protein MKI67, present during all active phases of the cell cycle (G1, S, G2, and mitosis), but is absent in resting cells (G0) [34]. Markers applied to detect neural stem/progenitor cells (NESTIN) and their commitment into neuronal (β-TUBULIN III, NF200, DOUBLE-CORTIN, MAP-2), astrocytic (GFAP) and oligodendroglial (PDGFRα, GalC) lineages have been used before in the study of our group [2,36,46] and are typical for characterization of neural lineages in vitro and in vivo [31]. It is important to note that the results of this study based on immunofluorescent images are only qualitative due to the high autofluorescence of the Col-DAC scaffolds (Figs.…”

A Platform for Studying Molecular and Cellular Mechanisms of Parkinson’s Disease Based on Human Induced Pluripotent Stem Cells

“…Neuronal differentiation according to the developed protocol takes about 40 days, and thereafter the cells may be maintained in the medium for maturation in the presence of BDNF, GDNF and ascorbic acid at least 40 days more. Differentiated cells were shown to express a characteristic marker for mature neuronssynaptophysin ( Figure 5 (a)), participating in the release of neuromediator [33]. The cultures of neurons obtained by us expressed also the marker of catecholaminergic (dopaminergic, in particular) neurons -tyrosine hydroxylase ( Figure 5 (b)).…”