Tight Junction Proteins ZO-1, Occludin, and Claudins in Developing and Adult Human Perineurium

Abstract

In peripheral nerves, groups of Schwann cell-axon units are isolated from the adjacent tissues by the perineurium, which creates a diffusion barrier responsible for the maintenance of endoneurial homeostasis. The perineurium is formed by concentric layers of overlapping, polygonal perineurial cells that form tight junctions at their interdigitating cell borders. In this study, employing indirect immunofluorescence and immunoelectron microscopy, we demonstrate that claudin-1 and -3, ZO-1, and occludin, but not claudin-2, -4, and -5, are expressed in the perineurium of adult human peripheral nerve. We also describe the expression of occludin, ZO-1, claudin-1, -3, and -5 in the developing human perineurium, showing that the expressions of claudin-1 and -3, ZO-1, and occludin follow similar spatial developmental expression patterns but follow different timetables in achieving their respective adult distributions. Specifically, claudin-1 is already largely restricted to perineurium-derived structures at 11 fetal weeks, whereas claudin-3 and occludin are weakly expressed in the perineurial structures at this age and acquire a well-defined perineurial distribution only between 22 and 35 fetal weeks. ZO-1 appears to acquire its mature profile even later during the third trimester. The results of the present and previous studies show that the perineurial diffusion barrier matures relatively late during human peripheral nerve development.

Tight Junction Proteins and Perineurial Cells in Neurofibromas

“…The small, seemingly normal nerve fascicles that traversed the neurofibromas expressed claudin-1, claudin-3, ZO-1, and occludin in perineurium ( Figures 2A, 2D, 2G, and 2J), which is in agreement with that reported for normal sciatic nerve (Pummi et al 2004). In the tumor tissue, the distribution of claudin-3 and ZO-1 was apparently the same as that of claudin-1 (Figures 2D-2I).…”

“…Occludin was not detectable between tumor cells and may be lacking from the TJs observed in neurofibromas. This is in contrast to normal human peripheral nerve where occludin is readily detected between perineurial cells (Pummi et al 2004). These findings suggest that neoplastic perineurial cells retain their capacity to form TJ-like junctions, which may not contain all of the same components as typical TJs.…”

“…We have recently characterized the expression of TJ components on developing and adult human peripheral nerve (Pummi et al 2004). The results showed that claudin-1, claudin-3, ZO-1, and occludin localized to the mature perineurium.…”

Transient opening of the perineurial barrier for analgesic drug delivery

“…The tight junction proteins claudin-1, claudin-5, and occludin are expressed in the perineurium and associated with permeability changes of the perineurium in a model of crush injury of the nerve (12,13). Hypertonic solutions have been used to open barriers to enhance drug delivery to the brain (14).…”

Tight Junction Proteins in Human Schwann Cell Autotypic Junctions

“…The non-compact structures include the paranodal loop regions, the Schmidt-Lanterman incisures, the periaxonal cytoplasmic collar, and the inner and outer mesaxons. At the nodes of Ranvier, interdigitations of the plasma membranes of adjacent Schwann cells assure the continuity of the Schwann cell sheath along the whole length of the axon, while a continuous, Schwann cell-derived basal lamina forms a permeable boundary between the endoneurial connective tissue layer and the Schwann cell myelin sheath (Thomas 1963).Perineurial cells of the perineurium form a selective diffusion barrier between the endoneurium and the epineurium (Thomas 1963;Jaakkola et al 1993;Pummi et al 2004), and we have previously shown that the tight junction (TJ) proteins zonula occludens (ZO)-1, occludin, claudin-1, and claudin-3 all contribute to the formation of this perineurial diffusion barrier in human Correspondence to: Sirkku Peltonen, …”