The Journal of comparative neurology
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Chronic nerve compression (CNC) injury initiates a series of pathological changes within the peripheral nerve at the site of injury. However, to date, little work has been performed to explore neuronal cell body responses to CNC injury. Here we show a preferential upregulation of growth-associated protein-43 (GAP-43) and enhanced Fluoro Ruby uptake by the small-diameter calcitonin gene-related protein (CGRP) and isolectin B4 (IB4)-positive neurons in the L4 and L5 ipsilateral dorsal root ganglion (DRG) 2 weeks and 1 month post injury. ⋯ Quantification of glial-derived neurotrophic factor (GDNF) protein revealed an upregulation in L4 and L5 DRG followed by a return to baseline values at later stages following injury. Upregulation of GDNF expression by Schwann cells was also readily apparent with both immunohistochemistry and Western blot analysis of 1 month compressed sciatic nerve specimens. Thus, CNC induces a phenotypic change in the DRG that appears to be temporally associated with increases in GDNF protein expression at and near the site of the compression injury in the nerve.
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Nogo receptors (NgR1, -2, and -3) and their ligands, i.e., myelin-derived neurite outgrowth inhibitor (Nogo)-A, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp), have been considered to play pivotal roles in controlling axonal regeneration and neuronal plasticity. We show here that NgR1-3 mRNAs were differentially expressed exclusively in neurons situated in the telencephalon, diencephalons, and cerebellum, whereas we could not detect any NgR1-3 mRNA expression in the mesencephalon, pons, medulla oblongata, and spinal cord. On the other hand, Nogo-A mRNA was abundantly expressed in both neurons and oligodendrocytes throughout the central nervous system (CNS). ⋯ Interestingly, we did not detect NgR1-3 mRNAs in monoaminergic neurons in the substantia nigra, ventral tegmental area, locus caeruleus, and raphe nuclei, which are known to have high regenerative capacity. In addition, although neurons in the reticular thalamus and cerebellar nuclei are also known to show high capacity for regeneration, NgR1-3 mRNAs were not detected there. These data indicate that NgR1-3, Nogo-A, MAG, and OMgp mRNAs are differentially expressed in the rat CNS and suggest that the level of NgR1-3 expression in a neuron might determine its regenerative capacity.