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Differential responses to odorant analogs after recovery from nerve transection.

We previously found that exposure-induced increase in odor sensitivity involves, at least in part, the olfactory epithelium. We did this by exposing mice to 5 alpha-androst-16-en-3-one (androstenone) and measuring changes in the epithelium. Past research showed that sensitivity to androstenone also could be induced by exposing individuals to 4-(4',4'-dimethylcyclohexyl)-2-methylcyclohexanone (DMCMC), a structural and functional analog of androstenone. What remained unknown is whether structural and/or functional odorant analogs share peripheral components. In the current work, we used a well-established model to disconnect the olfactory epithelium from the olfactory bulbs (BNX) to disrupt mechanisms underlying olfactory coding (when the afferents reinnervate the bulb, they do not synapse in their original glomeruli), and to examine the effects of disruption and restoration on exposure-induced odor sensitivity. In this study, we determined whether analogs of androstenone, viz., 5 alpha-androstan-3-one (androstanone) and DMCMC, could induce sensitivity to androstenone after BNX. Results demonstrate that exposure to either androstanone or DMCMC can induce sensitivity to androstenone in control mice. Different results were observed in mice that had recovered from bilateral BNX. Exposure to androstanone for 10 days immediately after surgery increased sensitivity to androstenone; however, exposure to DMCMC did not. These results suggest that androstanone and DMCMC, although apparent perceptual analogs of androstenone, may be using different pathways of olfaction within the central nervous system (CNS).

Androstenes↗

The terminal nerve and its relation with extrabulbar "olfactory" projections: lessons from lampreys and lungfishes.

The definition of the terminal nerve has led to considerable confusion and controversy. This review analyzes the current state of knowledge as well as diverging opinions about the existence, components, and definition of terminal nerves or their components, with emphasis on lampreys and lungfishes. I will argue that the historical terminology regarding this cranial nerve embraces a definition of a terminal nerve that is compatible with its existence in all vertebrate species. This review further summarizes classical and more recent anatomical, developmental, neurochemical, and molecular evidence suggesting that a multitude of terminalis cell types, not only those expressing gonadotropin-releasing hormone, migrate various distances into the forebrain. This results in numerous morphological and neurochemically distinct phenotypes of neurons, with a continuum spanning from olfactory receptor-like neurons in the olfactory epithelium to typical large ganglion cells that accompany the classical olfactory projections. These cell bodies may lose their peripheral connections with the olfactory epithelium, and their central projections or cell bodies may enter the forebrain at several locations. Since "olfactory" marker proteins can be expressed in bona fide nervus terminalis cells, so-called extrabulbar "olfactory" projections may be a collection of disguised nervus terminalis components. If we do not allow this pleiomorphic collection of nerves to be considered within a terminal nerve framework, then the only alternative is to invent a highly species- and stage-specific, and, ultimately, thoroughly confusing nomenclature for neurons and nerve fibers that associate with the olfactory nerve and forebrain.

Animals↗

The neurite growth promoting protease nexin 1 in glial cells of the olfactory bulb of the gerbil: an ultrastructural study.

The glia-derived serine protease inhibitor and neurite outgrowth promoter protease nexin-1 (PN-1) is expressed in Schwann cell precursors and astroblasts during embryogenesis. In the adult nervous system, PN-1 persists in the Schwann cells and olfactory glia only. Light-microscopic immunohistochemistry has revealed the presence of PN-1 in the olfactory mucosa and in the nerve fiber layer of the olfactory bulb. The present electron-microscopic study of the gerbil olfactory bulb confirms the occurrence of PN-1 in ensheathing cells of the olfactory nerve fiber layer, a special type of glia which envelopes olfactory axons. In addition, PN-1 is contained in typical astrocytes of the nerve fiber layer and of the glomerular layer. It is inferred that synthesis of PN-1 in the olfactory bulbs is maintained throughout adulthood because its neurite outgrowth promoting action is required for the continuous renewal of olfactory receptor neurons.

Amyloid beta-Protein Precursor↗

Apolipoprotein E is upregulated in olfactory bulb glia following peripheral receptor lesion in mice.

Apolipoprotein E (apoE), a lipid transporting protein, has been postulated to participate in nerve regeneration. To better clarify apoE function in the olfactory system, we evaluated the amount and distribution of apoE in the olfactory bulb following olfactory nerve lesion in mice. Olfactory nerve was lesioned in 2- to 4-month-old mice by intranasal irrigation with Triton X-100. Olfactory bulbs were collected at 0, 3, 7, 21, 42, and 56 days postlesion, and both apoE concentrations and apoE distribution were determined. ApoE levels, as determined by immunoblot analysis, were twofold greater than normal during nerve degeneration at 3 days. ApoE levels remained elevated by approximately 1.5 times normal levels at 7 through 21 days after injury and returned to baseline by 56 days. Immunocytochemical studies supported these observations. ApoE immunoreactivity was prominent on the olfactory nerve at 3 days after lesion and decreased to baseline levels at later time periods. Double-labeling immunocytochemical studies confirmed that both reactive astroglia and microglia produced detectable amounts of apoE following the lesion. Return of apoE expression to baseline paralleled measures of olfactory nerve maturation as measured by olfactory marker protein. These data suggest that apoE increases concurrent with nerve degeneration. ApoE may facilitate efficient regeneration perhaps by recycling lipids from degenerating fibers for use by growing axons. The association of apoE genotype with dementing illnesses may represent a diminished ability to support a lifetime of nerve regeneration.

Animals↗

Electron microscopic immunocytochemical localization of nerve growth factor in developing mouse olfactory neurons.

The immunocytochemical localization of nerve growth factor (NGF) in the embryonic mouse has been examined using correlative light and electron microscope procedures. In flat-embedded thick sections, primary sensory neurons of the olfactory pathway were clearly visible by their high level of NGF-like immunoreactivity. When ultrathin sections were examined under the electron microscope, the HRP reaction product present in the nasal epithelium was confined to the cytoplasm of the chemoreceptor cells, including the dendrites projecting into the nasal cavity. The axons projecting to the olfactory bulb and axon bundles within the bulb were also stained specifically for NGF. The reaction product did not appear to be associated with any particular subcellular structure. Neither the columnar supporting cells nor the basal precursor cells showed any evidence of immunoreactivity. No evidence was found for the presence of NGF in cells such as epithelial or glial cells within the immediate environment of the receptor neurons. These first subcellular localization studies indicate the presence of high levels of NGF in neurons not known to be sensitive to the trophic molecule.

Animals↗

Amphibian terminal nerve: distribution revealed by LHRH and AChE markers.

Immunocytochemical and histochemical studies in the tiger salamander and bullfrog demonstrated the presence of luteinizing hormone-releasing hormone-like immunoreactive (LHRH-ir) material and acetylcholinesterase (AChE) in the terminal nerve (TN). Immunoreactive perikarya and processes were found within the olfactory, vomeronasal and trigeminal nerves and in the nasal epithelium. Central TN projections consisted of fibers terminating in the olfactory bulb and bundles that projected to another group of LHRH-ir perikarya in the preoptic region. Up to 4 weeks following hypophysectomy, the labeling intensity and number of TN-immunoreactive neurons were not altered. Acetylcholinesterase histochemistry in the salamander revealed two distinct groups of neurons associated with the TN: a lightly labeled group of fusiform perikarya was located in the olfactory nerve proper and a more heavily labeled group of larger oval perikarya was found within AChE-positive trigeminal fascicles in the ventral mucosa. This study has demonstrated that the amphibian TN follows olfactory, vomeronasal and trigeminal nerves to reach peripheral targets in the nasal mucosa. The projection of TN fibers to discrete olfactory bulb glomeruli, especially evident in the bullfrog, suggests that the TN functions in odor processing. The TN projection to the preoptic region in both of these amphibians implicates the TN in reproductive processes.

Acetylcholinesterase↗

Retrograde transport of nerve growth factor from olfactory bulb to olfactory epithelium.

NGF is produced in the olfactory bulb and transported from the bulb to cholinergic neurons in the horizontal limb of the diagonal band. Although the expression of NGF receptors has been reported in olfactory epithelial cells, no correlation between NGF and olfactory epithelial cells has been found. This study aimed to define whether or not retrograde transport of NGF occurs in the olfactory neural system using the method of radioluminography. 125I-labeled NGF injected into the olfactory bulb was taken up and transported to the olfactory epithelium 18 h after injection. This finding suggests that bulbar NGF may act as a neurotrophic factor in olfactory epithelial cells.

Animals↗