Distinct subcellular localization of the neuronal marker HuC/D reveals hypoxia‐induced damage in enteric neurons

Abstract Background Correct neuronal identification is essential to study neurons in health and disease. Although commonly used as pan‐neuronal marker, HuC/D's expression pattern varies substantially between healthy and (patho)physiological conditions. This heterogenic labeling has received very little attention. We sought to investigate the subcellular HuC/D localization in enteric neurons in different conditions. Methods The localization of neuronal RNA ‐binding proteins HuC/D was investigated by immunohistochemistry in the mouse myenteric plexus using different toxins and caustic agents. Preparations were also stained with Sox10 and glial fibrillary acidic protein ( GFAP ) antibodies to assess enteric glial cell appearance. Key Results Mechanically induced tissue damage, interference with the respiratory chain and oxygen ( O 2 ) deprivation increased nuclear HuC/D immunoreactivity. This effect was paralleled by a distortion of the GFAP ‐labeled glial network along with a loss of Sox10 expression and coincided with the activation of a non‐apoptotic genetic program. Chemically induced damage and specific noxious stimuli did not induce a change in HuC/D immunoreactivity, supporting the specific nature of the nuclear HuC/D localization. Conclusions & Inferences HuC/D is not merely a pan‐neuronal marker but its subcellular localization also reflects the condition of a neuron at the time of fixation. The functional meaning of this change in HuC/D localization is not entirely clear, but disturbance in O 2 supply in combination with the support of enteric glial cells seems to play a crucial role. The molecular consequence of changes in HuC/D expression needs to be further investigated.