Neuroplasticity in the olfactory system: differential effects of central and peripheral lesions of the primary olfactory pathway on the expression of B-50/GAP43 and the olfactory marker protein.
The regeneration of the olfactory neuroepithelium following olfactory bulbectomy or peripheral deafferentation was studied with mRNA probes and antibodies for B-50/GAP43 and for olfactory marker protein (OMP). Two stages in the regeneration of the olfactory epithelium could be discerned with these reagents. The first stage occurs following either peripheral deafferentation of the olfactory epithelium with Triton X-100 (TX-100) or after bulbectomy and is characterized by the formation of a large population of immature olfactory receptor neurons. These newly formed neurons express B-50/GAP43, a phosphoprotein related to neuronal growth and plasticity. During the second stage of the regeneration process the newly formed olfactory neurons mature, as evidenced by a decrease in their expression of B-50/GAP43 and an increase in the expression of OMP. This stage is only manifested if the developing neurons have access to the target olfactory bulb. Formation of a full complement of OMP-expressing neurons occurs only after peripheral lesion with TX-100. In contrast, following bulbectomy the reconstituted olfactory epithelium lacks its normal target and is compromised in its ability to recover from nerve damage, as evidenced by the presence of a large number of B-50/GAP43-expressing neurons up to 3 months after the lesion and its failure to establish a full complement of OMP-expressing neurons. These results demonstrate that the olfactory epithelium is capable of replacing its sensory neurons independently of the presence of its target, the olfactory bulb. However, the differential patterns of expression of B-50/GAP43 and OMP at long times after peripheral lesion with TX-100 or bulbectomy illustrate the profound effect the olfactory bulb has on neuronal maturation in reconstituted olfactory neuroepithelium.
Verhaagen
J
J
Department of Neurosciences, Roche Institute of Molecular Biology, Nutley, New Jersey 07110.
Oestreicher
A B
AB
Grillo
M
M
Khew-Goodall
Y S
YS
Gispen
W H
WH
Margolis
F L
FL
D000818:Animals; D002490:Central Nervous System / Q000502:physiology*; D005260:Female; D019922:GAP-43 Protein; D005786:Gene Expression Regulation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity; D009693:Nucleic Acid Hybridization; D017830:Octoxynol; D009830:Olfactory Bulb / Q000378:metabolism / Q000502:physiology*; D051842:Olfactory Marker Protein; D009833:Olfactory Pathways / Q000378:metabolism / Q000502:physiology*; D011092:Polyethylene Glycols; D012333:RNA, Messenger / Q000378:metabolism*
D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D051842:Olfactory Marker Protein; C497598:Omp protein, mouse; D012333:RNA, Messenger; D011092:Polyethylene Glycols; D017830:Octoxynol