ABSTRACT
Lack of regeneration in the CNS has been attributed to many causes, including the presence of inhibitory molecules such as chondroitin sulfate proteoglycans (CSPGs). However, little is known about the contribution of CSPGs to regeneration failure in vivo, in particular at the dorsal root entry zone (DREZ), a unique CNS region that blocks regeneration of sensory fibers following dorsal root injury without glial scar formation. The goal of the present study was to evaluate the presence, regulation, and cellular identity of the proteoglycans Brevican, Neurocan, Versican V1 and Versican V2 in the DREZ using CSPG-specific antibodies and nucleic acid probes. Brevican and Versican V2 synthesized before the lesion were still present at high levels in the extracellular matrix of the DREZ several weeks after injury. In addition, Brevican was transiently expressed by reactive oligodendrocytes, and by a subset of astrocytes thereafter. Versican V2 mRNA appeared in NG2-positive cells with the morphology of oligodendrocyte precursor cells. Neurocan and Versican V1 levels were low before injury, and appeared in nestin-positive astrocytes and in NG2-positive cells, respectively, following lesion. Versican V1, but not V2, was also transiently increased in the peripheral dorsal root post-lesion. This is the first thorough description of the expression and cell association of individual proteoglycans following dorsal root lesion. It demonstrates that the proteoglycans Brevican, Neurocan, Versican V1, and Versican V2 are abundant in the DREZ at the time regenerating sensory fibers reach the PNS/CNS border and may therefore participate in growth-inhibition in this region.
Subject(s)
Chondroitin Sulfate Proteoglycans/genetics , Nerve Regeneration/physiology , Nerve Tissue Proteins/genetics , Spinal Nerve Roots/physiology , Animals , Astrocytes/physiology , Brevican , Cervical Vertebrae , Chondroitin Sulfate Proteoglycans/chemistry , Chondroitin Sulfate Proteoglycans/metabolism , Gene Expression , Isomerism , Lectins, C-Type , Mice , Mice, Inbred C57BL , Nerve Tissue Proteins/metabolism , Neurocan , Neurons, Afferent/cytology , Neurons, Afferent/physiology , RNA, Messenger/analysis , Rhizotomy , Spinal Cord/physiology , Spinal Nerve Roots/cytology , VersicansABSTRACT
The relative and absolute configuration of the title compound, (6R,7R,9R,11S)-16,17-didehydro-9-de-2-piperidinylormosanine, C15H24N2, has been elucidated. Two X-ray structures, one of the free base of the alkaloid and the second of its dihydrochloride monohydrate salt, C15H26N2(2+).2Cl-.H2O, have been determined to unequivocally establish the stereochemistry of aloperine, the parent member of a rare family of lupinine alkaloids.
