Immunohistochemical evidence for the brevican-tenascin-R interaction: Colocalization in perineuronal nets suggests a physiological role for the interaction in the adult rat brain

Abstract

Brevican is one of the most abundant chondroitin sulfate proteoglycans in the adult rat brain. We have recently shown that the C‐type lectin domain of brevican binds fibronectin type III domains 3–5 of tenascin‐R. Here we report strong evidence for a physiological basis for this interaction. Substantial brevican immunoreactivity was detected in a number of nuclei and in the reticular formations throughout the midbrain and hindbrain, including, but not limited to, the deep cerebellar nuclei, the trapezoid body, the red nucleus, the oculomotor nucleus, the vestibular nucleus, the cochlear nucleus, the gigantocellular reticular nucleus, the motor trigeminal nucleus, and the lateral superior olive. Most of the brevican immunoreactivity exhibited pericellular and reticular staining patterns. In almost all of these sites, brevican immunoreactivity colocalized with that of tenascin‐R, which was also substantially codistributed with versican, another member of the lectican family. Detailed analysis revealed that the pericellular staining of brevican resembled that in perineuronal nets in which tenascin‐R has been localized. Immunoelectron microscopy identified brevican immunoreactivity in the intercellular spaces surrounding presynaptic boutons and on their surfaces, but not in the synaptic clefts or in their immediate vicinity, a distribution pattern consistent with perineuronal nets. Taken together, our results provide strong evidence that the previously reported interactions between brevican and tenascin‐R may play a functional role within the perineuronal nets. J. Comp. Neurol. 410:256–264, 1999. © 1999 Wiley‐Liss, Inc.

Lecticans: organizers of the brain extracellular matrix

“…Yamaguchi, unpublished results], and in perineuronal nets of large neurons [47]. Versican is also detected in perineuronal nets [47,48]. In adult rat cerebellum, neurocan mRNA and immunoreactivity are detected in two types of cerebellar neurons, namely granule cells and Purkinje cells [74,75].…”

“…This pericellular staining has been identified to represent 'perineuronal nets', specialized extracellular matrices found predominantly in adult brain (see below for detail). These observations strongly suggest that the brevican-tenascin-R interaction is physiologically significant in the adult brain, though this notion does not exclude the possibility that other lecticans also bind tenascin-R in vivo, since they have also been observed in perineuronal nets [47][48][49]. Taken together, these observations suggest that tenascin-R is a physiological ligand for lecticans in the nervous system.…”

“…Second, natural brevican coimmunoprecipitates with tenascin-R from adult rat brain extracts [46]. Finally, brevican colocalizes with tenascin-R in a number of nuclei and reticular formations in the adult central nervous system [47]. In these sites, both brevican and tenascin-R show pericellular staining around cell bodies and proximal dendrites of large neurons.…”

“…In brain tissues, brevican is detected in association with neuroglial sheaths of velate protoplasmic astrocytes in the cerebellar granular layer [69], in immature oligodendrocytes of the hippocampal fimbria [T. Ogawa and Y. Yamaguchi, unpublished results], and in perineuronal nets of large neurons [47]. Versican is also detected in perineuronal nets [47,48].…”

“…Immunohistochemical studies demonstrated that a unique set of ECM molecules are present in PNN. Such molecules include lecticans (versican [31,47,48], brevican [47], neurocan [96], Cat-301 antigen [97]), DSD-1-PG [98], hyaluronan [99], tenascin-C [100] and tenascin-R [47,101]. It is intriguing to note that the two known ligands for lecticans, tenascin-R and hyaluronan, are components of PNN.…”