Research Progress of Olfactory Nerve Regeneration Mechanism and Olfactory Training

Figures & data

Table 1 Mechanism of Regeneration of the Olfactory Nerve

Type	Regulator	Effects	References
GBCs	Sox2	Proliferation of neuronal precursors, self-renewal	[^Citation9,Citation12,Citation13]
	Pax6	Differentiation, self-renewal	[^Citation13]
	Lgr5	Differentiation, self-renewal	[^Citation10,Citation11]
	Neurog1	Differentiation	[^Citation5]
	Neurod1	Differentiation	[^Citation5]
	Ascl1	Differentiation, proliferation	[^Citation14]
	Ascl3	Differentiation of Bowman’s glands cells	[^Citation47]
	Hes1	Differentiation of sustentacular cells	[^Citation14]
	p27	Proliferation	[^Citation8]
HBCs	Sox2	Differentiation	[^Citation9]
	Pax6	Differentiation	[^Citation9]
	TNF-α	Differentiation, proliferation	[^Citation18]
	CNTF	Differentiation, proliferation of GBCs	[^Citation20]
	p63	Inhibition	[^Citation22,Citation24]
	Hes1	Dormancy	[^Citation24]
OECs	GDNF	Axon growth, migration	[^Citation27^–^Citation29]
	Fibulin-3	Migration inhibition, proliferation	[^Citation30]
	Slit-2	Migration inhibition	[^Citation48]
	Nogo-66	Migration inhibition, adhesion	[^Citation49]
	TGF-β1	Phagocytosis	[^Citation33]
	S1P	Proliferation	[^Citation36]
	Wnt	Differentiation, proliferation	[^Citation35]
OB	BDNF	Differentiation, proliferation	[^Citation41,Citation42]
	NGF	Differentiation, proliferation	[^Citation40]
	NT-3	Enlargement	[^Citation43]
	ERK5	Maturation	[^Citation45]

Abbreviations: GBCs, globose basal cells; HBCs, horizontal basal cells; OECs, olfactory-ensheathing cells; OB, olfactory bulb; SOX2, sex determining region Y-box 2; Pax6, paired box; Lgr5, leucine-rich repeat-containing G-protein coupled receptor 5; Neurog1, neurogenin 1; Neurod1, neuronal differentiation factor 1; Ascl, achaete-scute complex-like; Hes1, hairy and enhancer of split 1; TNF-α, tumor necrosis factor-α; CNTF, ciliary neurotrophic factor; GDNF, glial cell-derived neurotrophic factor; Slit-2, slit guidance ligand 2; Nogo-66, extracellular domain with 66-amino-acid-residue of Nogo protein; TGF-β1, transforming growth factor-β1; S1P, sphingosine 1-phosphate; Wnt, Wingless-Int; BDNF, brain-derived neurotrophic factor; NGF, nerve growth factor; NT-3, neurotrophin 3; ERK5, extracellular regulated protein kinases 5.

Figure 1 Mechanism of regeneration of the olfactory nerve.

Figure 2 Mechanism of olfactory training in olfactory recovery.

Notes: 1. OT increases the activity of olfactory receptors and secretion of various neurotrophic factors to promote the proliferation and activation of neural precursor cells stimulates regeneration of the olfactory system in a stepwise manner. 2. OT stimulates the central nervous system and leads to an increase in the gray-matter volume and functional reorganization of olfactory-related brain regions, including the OB, piriform cortex (PC), amygdala (AM), insular cortex (IC), orbitofrontal cortex (OFC), entorhinal cortex (EC), hippocampus (H) and the thalamus (Th).

Abbreviations: OB, olfactory bulb; OE, olfactory epithelium; OR, olfactory receptors.

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