The telencephalon-associated intercellular adhesion molecule-5 (telencephalin; ICAM-5) regulates dendritic morphology in the developing brain. In vitro studies have shown that ICAM-5 is found predominantly within dendrites and immature dendritic protrusions, with reduced expression in mushroom spines, suggesting that ICAM-5 downregulation is critical for the maturation of synaptic structures. However, developmental expression of ICAM-5 has not been explored in depth at the ultrastructural level in intact brain tissue. To investigate the ultrastructural localization of ICAM-5 with transmission electron microscopy, we performed immunoperoxidase histochemistry for ICAM-5 in mouse visual cortex at postnatal day (P)14, a period of intense synaptogenesis, and at P28, when synapses mature. We observed the expected ICAM-5 expression in dendritic protrusions and shafts at both P14 and P28. ICAM-5 expression in these dendritic protrusions decreased in prevalence with developmental age to become localized predominantly to dendritic shafts by P28. To understand better the relationship between ICAM-5 and the endopeptidase metalloproteinase-9 (MMP-9), which mediates ICAM-5 cleavage following glutamate activation during postnatal development, we also explored ICAM-5 expression in MMP-9 null animals. This analysis revealed a similar expression of ICAM-5 in dendritic elements at P14 and P28; however, an increased prevalence of ICAM-5 was noted in dendritic protrusions at P28 in the MMP-9 null animals, indicating that, in the absence of MMP-9, there is no developmental shift in ICAM-5 subcellular localization. Our ultrastructural observations shed light on possible functions mediated by ICAM-5 and their regulation by extracellular proteases.
Keywords: ICAM-5; MMP-9; dendrite; electron microscopy; plasticity; telencephalin.
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