Olfactory System and Demyelination

Abstract

Within the central nervous system, the olfactory system represents one of the most exciting scenarios since it presents relevant examples of long-life sustained neurogenesis and continuous axonal outgrowth from the olfactory epithelium with the subsequent plasticity phenomena in the olfactory bulb. The olfactory nerve is composed of nonmyelinated axons with interesting ontogenetic interpretations. However, the centripetal projections from the olfactory bulb are myelinated axons which project to more caudal areas along the lateral olfactory tract. In consequence, demyelination has not been considered as a possible cause of the olfactory symptoms in those diseases in which this sense is impaired. One prototypical example of an olfactory disease is Kallmann syndrome, in which different mutations give rise to combined anosmia and hypogonadotropic hypogonadism, together with different satellite symptoms. Anosmin-1 is the extracellular matrix glycoprotein altered in the X-linked form of this disease, which participates in cell adhesion and migration, and axonal outgrowth in the olfactory system and in other regions of the central nervous system. Recently, we have described a new patho-physiological role of this protein in the absence of spontaneous remyelination in multiple sclerosis. In the present review, we hypothesize about how both main and satellite neurological symptoms of Kallmann syndrome may be explained by alterations in the myelination. We revisit the relationship between the olfactory system and myelin highlighting that minor histological changes should not be forgotten as putative causes of olfactory malfunction. Anat Rec, 296:1424Rec, 296: -1434Rec, 296: , 2013. V C 2013 Wiley Periodicals, Inc.Key words: myelin; lateral olfactory tract; olfactory bulb; Kallmann Syndrome; anosmin-1; FGFR1; FGF2; subventricular zone; multiple sclerosisAbbreviations used: AOB 5 accessory olfactory bulb; CNS 5 central nervous system; CR 5 cysteine-rich region; ECM 5 extracellular matrix; EGFR 5 epidermal growth factor receptor; FGF 5 fibroblast growth factor; FGFR1 5 fibroblast growth factor receptor-1; FnIII 5 fibronectin-like type III; HS 5 heparan sulphates; KS 5 Kallmann syndrome; LOT 5 lateral olfactory tract; MS 5 multiple sclerosis; OB 5 olfactory bulb; OEG 5 olfactory ensheathing glia; OPC 5 oligodendrocyte precursor cell; OSN 5 olfactory sensory neurons; PNS 5 peripheral nervous system; SVZ 5 forebrain subventricular zone; WAP 5 whey acidic protein; X-KS 5 X-linked Kallmann syndrome

Olfactory ensheathing cells from the nasal mucosa and olfactory bulb have distinct membrane properties

“…Guided by OECs, their axons fasciculate to form the first cranial nerve that projects to the olfactory bulb (OB). These axons, which are thin and unmyelinated (Garcia-Gonzalez, Murcia-Belmonte, Clemente, & De Castro, 2013), enter the OB within the outer nerve layer (ONL), where they continue to be wrapped by OECs. The axons then coalesce into large glomeruli where they relay with mitral and tufted cells.…”

Olfactory Pathology in Central Nervous System Demyelinating Diseases

“…Olfactory dysfunction is a common, but often overlooked, feature of multiple sclerosis (MS) . Even though MS is characterized by inflammatory demyelination disseminated throughout the central nervous system (CNS), evidence of olfactory bulb/tract demyelination is controversial.…”

Inflammatory olfactory neuropathy in two patients with Covid-19 

“…In ammation of the olfactory system and anosmia have been reported in other viral diseases 2 as was age-related atrophy of the olfactory epithelium 3 . The observed neuritis is most likely associated with axonal damage, as olfactory la lack myelin 4 . Sars-CoV-2-induced damage might be mediated by viral entry through its receptor angiotensin converting enzyme 2 and the transmembrane serine protease 2, which are expressed in non-neural cells of the olfactory epithelium 5 .…”