Objective: To investigate the effects of dopamine on olfactory function and inflammatory injury of olfactory bulb in mice with allergic rhinitis (AR). Methods: AR mouse model was established by using ovalbumin (OVA), and the mice were divided into two groups: olfactory dysfunction (OD) group and without OD group through buried food pellet test (BFPT). The OD mice were randomly divided into 2 groups, and OVA combined with dopamine (3, 6, 9 and 12 days, respectively) or OVA combined with an equal amount of PBS (the same treatment time) was administered nasally. The olfactory function of mice was evaluated by BFPT. The number of eosinophils and goblet cells in the nasal mucosa were detected by HE and PAS staining. Western blotting, immunohistochemistry or immunofluorescence were used to detect the expression of olfactory marker protein (OMP) in olfactory epithelium, the important rate-limiting enzyme tyrosine hydroxylase (TH) of dopamine, and the marker proteins glial fibrillary acidic protein (GFAP) and CD11b of glial cell in the olfactory bulb. TUNEL staining was used to detect the damage of the olfactory bulb. SPSS 26.0 software was used for statistical analysis. Results: AR mice with OD had AR pathological characteristics. Compared with AR mice without OD, the expression of OMP in olfactory epithelium of AR mice with OD was reduced (F=26.09, P<0.05), the expression of GFAP and CD11b in the olfactory bulb was increased (F value was 38.95 and 71.71, respectively, both P<0.05), and the expression of TH in the olfactory bulb was decreased (F=77.00, P<0.05). Nasal administration of dopamine could shorten the time of food globule detection in mice to a certain extent, down-regulate the expression of GFAP and CD11b in the olfactory bulb (F value was 6.55 and 46.11, respectively, both P<0.05), and reduce the number of apoptotic cells in the olfactory bulb (F=25.64, P<0.05). But dopamine had no significant effect on the number of eosinophils and goblet cells in nasal mucosa (F value was 36.26 and 19.38, respectively, both P>0.05), and had no significant effect on the expression of OMP in the olfactory epithelium (F=55.27, P>0.05). Conclusion: Dopamine can improve olfactory function in mice with AR to a certain extent, possibly because of inhibiting the activation of glial cells in olfactory bulb and reducing the apoptotic injury of olfactory bulb cells.
Animals ; Disease Models, Animal ; Dopamine ; Humans ; Mice ; Mice, Inbred BALB C ; Nasal Mucosa/metabolism* ; Olfactory Bulb/pathology* ; Ovalbumin ; Rhinitis, Allergic/metabolism*

Objective: To retrospectively analysely the electrophysiological and imaging features of isolated congenital anosmia (ICA) and to assess the clinical phenotypic characteristics and classification of ICA. Methods: Clinical data of 30 ICA patients in Beijing Anzhen Hospital from 2012 to 2019 was retrospectively reviewed, including 13 males and 17 females, aged (35±19) years. The control group consisted of 30 healthy people from medical examination center, including 13 males and 17 females, aged (39±14) years. The clinical characteristics of ICA were analyzed using Sniffin' Sticks test, olfactory event-related potentials (oERPs), trigeminal event-related potentials (tERP) and olfactory pathway MRI. SPSS 17.0 software was used to compare the difference of olfactory function between the two groups. The correlation between olfactory bulb, olfactory sulcus structure and age was observed, and the clinical phenotype characteristics of ICA patients were analyzed. Results: The subjective olfactory function was completely lost in ICA patients. oERP was absent in all of the ICA patients, but showed normal N₁ and P₂ waves in controls. tERP could be evoked in 63.3% (19/30) of ICA patients, and signals in these patients showed higher amplitude in the N₁ ((-10.33±6.93) μV vs (-5.11±2.71) μV, t=-10.113, P<0.01) and P₂ ((+17.25±8.51) μV vs (+7.31±3.46) μV, t=5.443, P<0.01) waves than that of the controls. Olfactory bulbs were aplastic in 80.0% (24/30) of patients and hypoplastic in 20.0% (6/30) of patients. Fifty-six point seven percent (17/30) of patients had bilateral olfactory sulcus deletion while 43.3% (13/30) had dysplasia, and all of the patients exhibited a depth of olfactory sulcus less than 8 mm. Both the structure of olfactory bulbs and olfactory sulcus were not associated with age for ICA patients (r value was -0.174 and 0.325, respectively, all P>0.05). Conclusions: ICA patients show neurophysiologic deficits and some anatomic differences compared with healthy controls. The absence of oERP combining with a depth of olfactory sulcus less than 8 mm is the important indicator for clinical diagnosis of ICA. The structure of olfactory bulb may be a critical factor for clinical classification of ICA.
Adolescent ; Adult ; Anosmia ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Olfaction Disorders/diagnosis* ; Olfactory Bulb/diagnostic imaging* ; Olfactory Pathways ; Retrospective Studies ; Smell ; Young Adult

Objective: To report the case of a woman who underwent smell training for post-infectious olfactory dysfunction presumably from COVID-19. Methods: Design: Case Report. Setting: Tertiary Private Training Hospital. Patient: One. Result: A 41-year-old woman who developed olfactory dysfunction attributed to COVID-19 underwent smell training. At baseline, her responses were mostly “no smell,” and those reported as “can smell a bit” were rated as distorted. After three months, she could now smell items that she previously could not smell, but these smells were still distorted. At the time of this writing, she was on her 4th month of smell training. Conclusion Although we cannot rule out spontaneous resolution of anosmia in our patient, we would like to think that smell training contributed to her recovery of smell.
Anosmia ; Anosmia ; Olfactory Bulb ; Olfaction Disorders

Olfactory dysfunction occurs in multiple sclerosis in humans, as well as in an animal model of experimental autoimmune encephalomyelitis (EAE). The aim of this study was to analyze differentially expressed genes (DEGs) in olfactory bulb of EAE-affected mice by next generation sequencing, with a particular focus on changes in olfaction-related signals. EAE was induced in C57BL/6 mice following immunization with myelin oligodendrocyte glycoprotein and adjuvant. Inflammatory lesions were identified in the olfactory bulbs as well as in the spinal cord of immunized mice. Analysis of DEGs in the olfactory bulb of EAE-affected mice revealed that 44 genes were upregulated (and which were primarily related to inflammatory mediators), while 519 genes were downregulated; among the latter, olfactory marker protein and stomatin-like 3, which have been linked to olfactory signal transduction, were significantly downregulated (log2 [fold change] >1 and p-value < 0.05). These findings suggest that inflammation in the olfactory bulb of EAE-affected mice is associated with the downregulation of some olfactory signal transduction genes, particularly olfactory marker protein and stomatin-like 3, which may lead to olfactory dysfunction in an animal model of human multiple sclerosis.
Animals ; Down-Regulation ; Encephalomyelitis, Autoimmune, Experimental ; Gene Expression ; Humans ; Immunization ; Inflammation ; Mice ; Models, Animal ; Multiple Sclerosis ; Myelin-Oligodendrocyte Glycoprotein ; Olfactory Bulb ; Olfactory Marker Protein ; Signal Transduction ; Spinal Cord ; Transcriptome

OBJECTIVES: Parkinson disease (PD) is frequently associated with olfactory disorder at early stage, which is caused by deposition of Lewy bodies emerging from the olfactory bulb to higher olfactory centers. Early detection of olfactory disorder in the patients with PD may lead to the early diagnosis and treatment for this refractory disease. METHODS: Visual analog scale (VAS), Jet Stream Olfactometry, and Japanese smell identification test, Open Essence (OE), were carried out on 39 patients with PD. Thirty-one patients with postviral olfactory disorder (PVOD), which was caused by the olfactory mucosal dysfunction, were also enrolled in this study as control. RESULTS: There were no significant differences in detection thresholds (2.2 vs. 1.4, P=0.13), recognition thresholds (3.9 vs. 3.5, P=0.39) and OE (4.8 vs. 4.2, P=0.47) between PVOD and PD, while VAS scores of PVOD and PD were significantly different (2.0 and 6.2, P<0.01). In OE, significant differences were observed in the accuracy rates of menthol (68% vs. 44%, P=0.04) and Indian ink (42% vs. 15%, P=0.01) between PVOD and PD. Of particular interest, patients with PVOD tended to select “no detectable,” while patients with PD tended to select wrong alternative other than “no smell detected.” CONCLUSION: Discrepancy between VAS and OE, and high selected rates of wrong alternative other than “undetectable” in OE might be significant signs of olfactory dysfunction associated with PD.
Asian Continental Ancestry Group ; Early Diagnosis ; Humans ; Ink ; Lewy Bodies ; Menthol ; Olfactometry ; Olfactory Bulb ; Parkinson Disease ; Rivers ; Smell ; Visual Analog Scale

Parkinson's disease (PD) is a common neurodegenerative disorder arising from an interplay between genetic and environmental risk factors. Studies have suggested that the pathological hallmarks of intraneuronal α-synuclein aggregations may start from the olfactory bulb and the enteric nervous system of the gut and later propagate to the brain via the olfactory tract and the vagus nerve. This hypothesis correlates well with clinical symptoms, such as constipation, that may develop up to 20 years before the onset of PD motor symptoms. Recent interest in the gut–brain axis has led to vigorous research into the gastrointestinal pathology and gut microbiota changes in patients with PD. In this review, we provide current clinical and pathological evidence of gut involvement in PD by summarizing the changes in gut microbiota composition and gut inflammation associated with its pathogenesis.
Brain ; Constipation ; Enteric Nervous System ; Gastrointestinal Microbiome ; Humans ; Inflammation ; Microbiota ; Neurodegenerative Diseases ; Olfactory Bulb ; Parkinson Disease ; Pathology ; Risk Factors ; Vagus Nerve

The olfactory system can detect many odorants with high sensitivity and selectivity based on the expression of nearly a thousand types of olfactory receptors (ORs) in olfactory receptor neurons (ORNs). These ORs have a dynamic odorant detection range and contribute to signal encoding processes in the olfactory bulb (OB). To harness the capabilities of the olfactory system and develop a biomimetic sensor, stable culture and maintenance of ORNs are required. However, in vitro monolayer culture models have several key limitations: i) short available period of cultured neurons, ii) low cultural efficiency, and iii) long-term storage challenges. This study aims to develop a technique: i) to support the spheroid culture of primary ORN precursors facilitating stable maintenance and long-term storage, and ii) to demonstrate the viability of ORN spheroid culture in developing an olfactory system mimetic bioelectronic nose. Recombinant protein (REP; TGPG[VGRGD(VGVPG)₆]₂₀WPC) was used to form the ORN spheroids. Spheroid formation enabled preservation of primary cultured ORNs without a significant decrease in viability or the expression of stemness markers for ten days. Physiological characteristics of the ORNs were verified by monitoring intracellular calcium concentration upon odorant mixture stimulation; response upon odorant stimulation were observed at least for ten days in these cultivated ORNs differentiated from spheroids. Coupling ORNs with multi electrode array (MEA) enabled the detection and discrimination of odorants by analyzing the electrical signal patterns generated following odorant stimulation. Taken together, the ORN spheroid culture process is a promising technique for the development of a bioelectronic nose and high-throughput odorant screening device.
Biomimetics ; Calcium ; Discrimination (Psychology) ; Electrodes ; In Vitro Techniques ; Mass Screening ; Neurons ; Nose* ; Odors ; Olfactory Bulb ; Olfactory Receptor Neurons*

OBJECTIVE: To observe the effects of treatment on the ultrastructure of olfactory bulb and the expression of substantia nigra glial fibrillary acidic protein (GFAP) in mice with Parkinson's disease (PD) induced by lipopolysaccharide (LPS), and to provide methods and evidence for early prevention and treatment of PD. METHODS: Forty C57BL/6 male mice were randomly divided into a blank group, a model group, an electroacupuncture (EA) group and a medication group, 10 mice in each one. The mice in the model group, EA group and medication group were treated with 30-day nasal perfusion of LPS to establish PD model. From the first day of model establishment, the mice in the EA group were treated with electroacupuncture at bilateral "Yingxiang" (LI 20) and "Yintang" (GV 29) for 20 min, once a day; 5-day treatment was taken as one session, and 4 sessions were given with an interval of 2 days between sessions. The mice in the medication group were treated with intraperitoneal injection of L-DOPA, 10 mg/mL, once a day; 5-day treatment was taken as one session, and 4 sessions were given with an interval of 2 days between sessions. After treatment, the behavioristics changes were observed by using footprint analysis and swimming test score; the ultrastructure of olfactory bulb was observed by using transmission electron microscopy; the expression of GFAP in substantia nigra was measured by using western blot method. RESULTS: ① After model establishment, the mice in the model group, the EA group and medication group showed significant symptoms of quiver and fear of chill, and the BMI was significantly lower than that in the blank group (all <0.05). The results of behavioristics test indicated footprint length and swimming time in the model group, the EA group and medication group was significantly lower than those in the blank group (all <0.01), indicating the successful establishment of PD model. ② After one-session treatment, the symptoms of quiver and fear of chill were not observed in the EA group. After 4-session treatment, the BMI in the EA group was significantly higher than that in the model group (<0.05); the symptoms of quiver and fear of chill were not observed in the medication group, but the BMI was similar with the model group (>0.05). ③ After treatment, the footprint and swimming time in the model group were significantly lower than that in the blank group (both <0.01); the footprint and swimming time in the EA group and medication group were significantly higher than those in the model group (all <0.01).④ After treatment, compared with the blank group, the organelles and ultrastructure of olfactory bulb in the model group were significantly improved; the ultrastructure of olfactory bulb in the EA group was improved compared with that in the model group. ⑤ After treatment, the expression of substantia nigra GFAP in the model group was significantly higher than that in the blank group (<0.01); the expression of substantia nigra GFAP in the EA group and medication group was significantly lower than that in the model group (both <0.05). CONCLUSION The early treatment of can improve behavioral disorders in LPS-induced early PD mice, and the mechanism may be related to the regulation of olfactory disorders and the expression of GFAP in substantia nigra.
Animals ; Electroacupuncture ; Glial Fibrillary Acidic Protein ; Male ; Mice, Inbred C57BL ; Olfactory Bulb ; Parkinson Disease ; Rats ; Rats, Sprague-Dawley

BACKGROUND: The olfactory bulb is anatomically exposed and thus can be directly damaged by external stimulation. This can occur as an occupational injury owing to contact with organic solvents or other causes. We present cases of eight patients who sustained occupation-related exposure to potentially toxic substances and later presented with signs and symptoms of anosmia. We examined the occupational and medical characteristics of the patients and evaluated their work-relatedness. CASE PRESENTATION: Case 1: A 50-year-old man performed high-frequency heat treatments for approximately 11 years. He experienced decreased senses for olfaction and taste during the later years culminating in the diagnosis of anosmia after 3 years (high work-relatedness). Case 2: A 54-year-old man whose work involved exposure to various organic solvents, such as spray painting and application of paint and thinners for approximately 4 years, was subsequently diagnosed with anosmia based on rhinorrhea, headache, and loss of olfaction (high work-relatedness). Case 3: A 44-year-old-man who performed spray painting for approximately 17 years developed anosmia (high work-relatedness). Case 4: A 44-year-old man was involved in ship engine cleaning once a month, for approximately 7 h per cleaning session; he was diagnosed with anosmia based on loss of olfaction (low work-relatedness). Case 5: A 41-year-old man worked in ship building block construction for approximately 13 years; anosmia diagnosis was based on loss of olfaction (low work-relatedness). Case 6: A 47-year-old woman performed product inspection and labeling at a plant manufacturing automobile parts; anosmia diagnosis was based on decreased olfaction and taste (low work-relatedness). Case 7: A 50-year-old woman performed epoxy coating in a plant manufacturing automobile parts; anosmia diagnosis was based on diminishing olfaction (low work-relatedness). Case 8: A 57-year-old woman performed cleaning of the area where mobile phone parts were manufactured; anosmia diagnosis was based on diminishing olfaction (low work-relatedness). CONCLUSION: The study results confirmed work-relatedness when the subject was young, and the duration of exposure was long without any other cause of anosmia. Regarding compensation for occupational diseases, work-relatedness can be recognized as a relative concept.
Adult ; Automobiles ; Cell Phones ; Compensation and Redress ; Diagnosis ; Female ; Headache ; Hot Temperature ; Humans ; Middle Aged ; Occupational Diseases ; Occupational Injuries ; Olfaction Disorders ; Olfactory Bulb ; Paint ; Paintings ; Plants ; Ships ; Smell ; Solvents

The hippocampus and olfactory bulb incorporate new neurons migrating from neurogenic regions in the brain. Hippocampal atrophy is evident in numerous neurodegenerative disorders, and altered hippocampal neurogenesis is an early pathological event in Alzheimer's disease. We hypothesized that hippocampal neurogenesis is affected by olfactory stimuli through the neural pathway of olfaction-related memory. In this study, we exposed mice to novel pleasant odors for three weeks and then assessed the number of neurons, non-neuronal cells (mainly glia) and proliferating cells in the hippocampus and olfactory bulb, using the isotropic fractionator method. We found that the odor enrichment significantly increased the neuronal cell numbers in the hippocampus, and promoted cell proliferation and neurogenesis in the olfactory bulb. In contrast, the glial cell numbers remained unchanged in both of the regions. Our results suggest that exposure to novel odor stimuli promotes hippocampal neurogenesis and support the idea that enriched environments may delay the onset or slow down the progression of neurodegenerative disorders.
Alzheimer Disease ; Animals ; Atrophy ; Brain ; Cell Count ; Cell Proliferation ; Hippocampus ; Memory ; Methods ; Mice* ; Neural Pathways ; Neurodegenerative Diseases ; Neurogenesis ; Neuroglia ; Neurons* ; Odors* ; Olfactory Bulb