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

Abstract

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.

Targeted Overexpression of the Neurite Growth-Associated Protein B-50/GAP-43 in Cerebellar Purkinje Cells Induces Sprouting after Axotomy But Not Axon Regeneration into Growth-Permissive Transplants

“…The preparation of radiolabeled antisense B-50/ GAP-43 RNA probe and the procedures used for in situ hybridization were performed as described previously (Verhaagen et al, 1990). Tenmicrometer-thick paraformaldehyde-fixed sections were mounted on poly-L-lysine-coated microscope slides.…”

Neuronal regeneration: Lessons from the olfactory system

“…. reappearance of immature neurons is much faster in the bulbectomy model than when the OE is damaged physically by irrigation with Triton X-100, 46 presumably because neuronal progenitor cells are not damaged by the bulbectomy procedure, whereas, all cell types are damaged indiscriminately by Triton X-100 irrigation. However, the OE fully recovers following Triton treatment, regaining its full complement of mature ORNs.…”

“…X-100 or inhalation of methyl bromide MeBr gas also cause major physical damage to the OE, although regeneration following these methods of damage is usually much more robust than that following zinc sulfate treatment. 46,47 Within 1 day following MeBr injury to the OE, most of the cells in the OE disappear, and the epithelium is only 1᎐2 cells thick. 47 This is followed by an increase in cell proliferation beginning 1᎐2 days following injury, which peaks at approximately 1 week post-lesion and remains at high levels for at least 4 weeks following exposure to the gas.…”

“…However, the OE fully recovers following Triton treatment, regaining its full complement of mature ORNs. 46 Recovery of the mature neurons is not seen following bulbectomy, since ORNs are deprived of the ability to make functional connections with the bulb, and such connection appears to be required for ORN maturation and survival. 11,28,46 Another result of bulbectomy is that the levels of both ORN apoptosis and progenitor cell proliferation are permanently upregulated in the OE ipsilateral to the lesion.…”

“…46 Recovery of the mature neurons is not seen following bulbectomy, since ORNs are deprived of the ability to make functional connections with the bulb, and such connection appears to be required for ORN maturation and survival. 11,28,46 Another result of bulbectomy is that the levels of both ORN apoptosis and progenitor cell proliferation are permanently upregulated in the OE ipsilateral to the lesion. 13,28,33,50 The increase in neuronal apoptosis is presumably a reflection of the increased turnover of ORNs unable to make synaptic connections with the olfactory bulb.…”