Functional organization of olfactory system.

Neurochemistry of the vertebrate olfactory bulb

the connections of the mouse olfactory bulb: A study using orthograde and retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase

Occupational exposures to inhalation of certain metal dusts or aerosols can cause loss of olfactory acuity, atrophy of the nasal mucosa, mucosal ulcers, perforated nasal septum, or sinonasal cancer. Anosmia and hyposmia have been observed in workers exposed to Ni- or Cd-containing dusts in alkaline battery factories, nickel refineries, and cadmium industries. Ulcers of the nasal mucosa and perforated nasal septum have been reported in workers exposed to Cr(VI) in chromate production and chrome plating, or to As(III) in arsenic smelters. Atrophy of the olfactory epithelium has been observed in rodents following inhalation of NiSO4 or alphaNi3S2. Cancers of the nose and nasal sinuses have been reported in workers exposed to Ni compounds in nickel refining, cutlery factories, and alkaline battery manufacture, or to Cr(VI) in chromate production and chrome plating. In animals, several metals (eg, Al, Cd, Co, Hg, Mn, Ni, Zn) have been shown to pass via olfactory receptor neurons from the nasal lumen through the cribriform plate to the olfactory bulb. Some metals (eg, Mn, Ni, Zn) can cross synapses in the olfactory bulb and migrate via secondary olfactory neurons to distant nuclei of the brain. After nasal instillation of a metal-containing solution, transport of the metal via olfactory axons can occur rapidly, within hours or a few days (eg, Mn), or slowly over days or weeks (eg, Ni). The olfactory bulb tends to accumulate certain metals (eg, Al, Bi, Cu, Mn, Zn) with greater avidity than other regions of the brain. The molecular mechanisms responsible for metal translocation in olfactory neurons and deposition in the olfactory bulb are unclear, but complexation by metal-binding molecules such as carnosine (beta-alanyl-L-histidine) may be involved.

/pdf/nasal-toxicity-carcinogenicity-and-olfactory-uptake-of-53nb3wd7vl.pdf

Nasal Toxicity, Carcinogenicity, and Olfactory Uptake of Metals

The characteristics of the islands of Calleja complex (ICC) in the basal forebrain of the rat were studied with immunohistochemistry, histofluorescence, acetylcholinesterase staining, India ink vascular perfusions, electron microscopy, and steroid autoradiography. The ICC contains clusters of granule cells and associated medium-sized and large cells in the surrounding neuropil of the olfactory tubercle and septum-nucleus accumbens interface. The ICCs were found to contain monoamine fibers (dopamine and norepi-nephrine), neuroactive peptide fibers (leu-enkephalin, met-enkephalin, substance P, cholecystokinin, luteinizing hormone-releasing hormone), acetyl-cholinesterase-containing somata and dendrites, and medium-sized and large cells that concentrate [3H] estradiol.



The specific overlap and combination of putative neurotransmitters in separate compartments of the ICC suggest that these structures contain striatum- and pallidumlike components. Striatumlike regions are defined as the zone in the rim regions of the ICC and are innervated predominantly by dopamine and cholecystokinin inputs. Pallidumlike regions are defined as the synaptic zone near the medium-sized and large cells of the cap and core regions of the ICC and they are innervated predominantly by enkephalin, substance P, and gamma aminobutyric acid inputs. The morphology, connections, and neurotransmitter relationships of the ICC, therefore, resemble classical Striatopallidal systems.



The additional presence of substances involved in the reproductive neuroendocrine systems (luteinizing hormone-releasing hormone, estradiol-binding cells), especially in the medial ICC, suggest that some ICC are involved in an endocrine corticostriatopallidal system. These endocrine systems resemble other neocortically and allocortically originating corticostriatopallidal systems in terms of their cell types, connections, and neurotransmitter systems. A functional role for the ICC in extrapyramidal motor systems is proposed.

The islands of Calleja complex of rat basal forebrain. III. Histochemical evidence for a striatopallidal system.

Previous in vivo studies have shown that beta-alanine is incorporated specifically into the dipeptide L-carnosine (beta-alanyl-L-histidine). In the present study, we administered beta-[3H]alanine to the nasal cavity of hamsters and used biochemical analyses to identify the radioactively labeled compounds in the olfactory epithelium and olfactory bulb and autoradiography to demonstrate the localization and transport of the label in the primary afferents of the olfactory system. The olfactory epithelium and lamina propria were labeled intensely 6 hr after intranasal beta-[3H]alanine administration. At this survival time, 61% of the radioactivity in the olfactory epithelium was present in the carnosine fraction, while 37% of the label remained in the beta-alanine fraction. After 24-hr and 4-day survival periods, greater than 82% of the radioactivity was present in the carnosine fraction, and the olfactory receptors and bundles of axons were labeled preferentially. The olfactory nerve and glomerular layers of the main olfactory bulb were labeled intensely at 6 and 24 hr after beta-[3H]alanine administration; much less label was present in these layers at 4 days survival. At all three of these survival times, greater than 84% of the radioactivity in the olfactory bulb was present in the carnosine fraction. No label was present in the olfactory epithelium or bulb 18 days after beta-[3H]alanine administration. While the autoradiographic labeling over the structures of the accessory olfactory system was consistently less intense than that over the main olfactory system structures, the patterns of labeling were similar over the four survival times. Intranasal alpha-[3H]alanine administration resulted in some labeling in the primary afferent fibers, but the labeling did not have the specificity nor the same time course over the four survival times that was observed after beta-[3H]alanine administration. The results are consistent with the hypothesis that carnosine is a neurotransmitter or neuromodulator in the olfactory neurons. The results also suggest that carnosine may play a similar role in the vomeronasal neurons.

https://www.jneurosci.org/content/jneuro/2/2/244.full.pdf

Carnosine in primary afferents of the olfactory system: an autoradiographic and biochemical study

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Carnosine in primary afferents of the olfactory system: an autoradiographic and biochemical study