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Chemical Senses Apr 2020Estrogen has been shown to affect differentiation and proliferation as a mitogen in various neural systems. Olfactory receptor cells are unique within the nervous...
Estrogen has been shown to affect differentiation and proliferation as a mitogen in various neural systems. Olfactory receptor cells are unique within the nervous system, and have the ability to regenerate even after an individual has reached maturity. Olfactory receptor cells also regenerate after experimentally induced degeneration. The purpose of this study is to observe the influence of estrogen depletion induced by ovariectomy on olfactory nerve regeneration. Female mice underwent bilateral ovariectomy at 8 weeks of age and received intraperitoneal administration of methimazole 1 week later. At 2, 4, and 6 weeks after methimazole administration, the olfactory mucosa was analyzed histochemically to determine olfactory epithelium (OE) thickness, olfactory marker protein distribution, and Ki-67 immunoreactivity. Furthermore, 2 weeks after ovariectomy, trkA protein distribution in the OE and nerve growth factor (NGF) levels in the olfactory bulb were determined by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. Our results showed that in ovariectomized mice OMP, Ki-67, and trkA-immunopositive cells expression decreased at 2 weeks after methimazole injection, a time point at which regeneration is underway. At this same time point, although NGF production in the olfactory bulb had increased before methimazole administration, no differences were observed between the ovx and control groups. These results suggest that estrogen depletion induces a suppressive effect on regeneration of olfactory neurons, and that estrogen may have a potential use in the treatment of sensorineural olfactory dysfunction.
Topics: Animals; Estrogens; Female; Mice; Mice, Inbred BALB C; Nerve Regeneration; Olfactory Bulb; Olfactory Mucosa; Olfactory Nerve; Ovariectomy
PubMed: 32010939
DOI: 10.1093/chemse/bjaa005 -
Aging Cell Apr 2023Olfactory dysfunction is a prevalent symptom and an early marker of age-related neurodegenerative diseases in humans, including Alzheimer's and Parkinson's Diseases....
Olfactory dysfunction is a prevalent symptom and an early marker of age-related neurodegenerative diseases in humans, including Alzheimer's and Parkinson's Diseases. However, as olfactory dysfunction is also a common symptom of normal aging, it is important to identify associated behavioral and mechanistic changes that underlie olfactory dysfunction in nonpathological aging. In the present study, we systematically investigated age-related behavioral changes in four specific domains of olfaction and the molecular basis in C57BL/6J mice. Our results showed that selective loss of odor discrimination was the earliest smelling behavioral change with aging, followed by a decline in odor sensitivity and detection while odor habituation remained in old mice. Compared to behavioral changes related with cognitive and motor functions, smelling loss was among the earliest biomarkers of aging. During aging, metabolites related with oxidative stress, osmolytes, and infection became dysregulated in the olfactory bulb, and G protein coupled receptor-related signaling was significantly down regulated in olfactory bulbs of aged mice. Poly ADP-ribosylation levels, protein expression of DNA damage markers, and inflammation increased significantly in the olfactory bulb of older mice. Lower NAD levels were also detected. Supplementation of NAD through NR in water improved longevity and partially enhanced olfaction in aged mice. Our studies provide mechanistic and biological insights into the olfaction decline during aging and highlight the role of NAD for preserving smelling function and general health.
Topics: Humans; Mice; Animals; Smell; Olfaction Disorders; Mice, Inbred C57BL; NAD; Aging; DNA Damage; Olfactory Bulb; Inflammation
PubMed: 36846960
DOI: 10.1111/acel.13793 -
The Journal of Neuroscience : the... Feb 2023The accessory olfactory system (AOS) is critical for the development and expression of social behavior. The first dedicated circuit in the AOS, the accessory olfactory...
The accessory olfactory system (AOS) is critical for the development and expression of social behavior. The first dedicated circuit in the AOS, the accessory olfactory bulb (AOB), exhibits cellular and network plasticity in male and female mice after social experience. In the AOB, interneurons called internal granule cells (IGCs) express the plasticity-associated immediate-early gene following intermale aggression or mating. Here, we sought to better understand how -expressing IGCs shape AOB information processing and social behavior in the context of territorial aggression. We used "ArcTRAP" (Arc-CreERT2) transgenic mice to selectively and permanently label -expressing IGCs following male-male resident-intruder interactions. Using whole-cell patch-clamp electrophysiology, we found that -expressing IGCs display increased intrinsic excitability for several days after a single resident-intruder interaction. Further, we found that -expressing IGCs maintain this increased excitability across repeated resident-intruder interactions, during which resident mice increase or "ramp" their aggression. We tested the hypothesis that -expressing IGCs participate in ramping aggression. Using a combination of ArcTRAP mice and chemogenetics (Cre-dependent hM4D(G)-mCherry AAV injections), we found that disruption of -expressing IGC activity during repeated resident-intruder interactions abolishes the ramping aggression exhibited by resident male mice. This work shows that -expressing AOB IGC ensembles are activated by specific chemosensory environments, and play an integral role in the establishment and expression of sex-typical social behavior. These studies identify a population of plastic interneurons in an early chemosensory circuit that display physiological features consistent with simple memory formation, increasing our understanding of central chemosensory processing and mammalian social behavior. The accessory olfactory system plays a vital role in rodent chemosensory social behavior. We studied experience-dependent plasticity in the accessory olfactory bulb and found that internal granule cells expressing the immediate-early gene after the resident-intruder paradigm increase their excitability for several days. We investigated the roles of these -expressing internal granule cells on chemosensory social behavior by chemogenetically manipulating their excitability during repeated social interactions. We found that inhibiting these cells eliminated intermale aggressive ramping behavior. These studies identify a population of plastic interneurons in an early chemosensory circuit that display physiological features consistent with simple memory formation, increasing our understanding of central chemosensory processing and mammalian social behavior.
Topics: Mice; Male; Female; Animals; Olfactory Bulb; Interneurons; Neurons; Social Behavior; Aggression; Mice, Transgenic; Mammals
PubMed: 36623874
DOI: 10.1523/JNEUROSCI.0847-22.2022 -
European Archives of... Mar 2023Cigarette smoking remains a serious health problem all over the world. We investigated the peripheral and central olfactory pathways in young male smokers to determine...
OBJECTIVES
Cigarette smoking remains a serious health problem all over the world. We investigated the peripheral and central olfactory pathways in young male smokers to determine whether there is a relationship between the amount of cigarettes smoked and duration of smoking and the dimensions of the olfactory areas.
METHODS
In this retrospective study, cranial Magnetic Resonance Imaging (MRI) images of adult male smokers aged ≤ 40 years (n = 51) and 50 healthy male adults were analyzed. The olfactory bulbus (OB) volumes and olfactory sulcus (OS) depths, insular gyrus, and corpus amygdala areas were measured via cranial MRI. In the smoker group, the number of cigarettes smoked and duration of smoking were noted and the Brinkmann index was calculated.
RESULTS
OB volume, OS depth, and the insular gyrus areas of the smokers were lower than in the control group (p < 0.05). There were no differences between the groups in terms of the corpus amygdala measurements (p > 0.05). No significant correlations were found between the number of cigarettes smoked daily, smoking duration, and the Brinkmann index and the peripheral and central olfactory measurements in our study (p > 0.05).
CONCLUSIONS
In smokers, OB volumes, the OS, and the central areas decrease bilaterally, regardless of smoking duration and number of cigarettes smoked daily. This could be related to inflammatory mediators that may be harmful to the olfactory neuroepithelium, gray matter atrophy in the brain, or endothelial damage related to smoking and its effects on blood support to the brain and olfactory regions.
Topics: Adult; Humans; Male; Smokers; Olfaction Disorders; Retrospective Studies; Smell; Magnetic Resonance Imaging; Olfactory Bulb
PubMed: 36242611
DOI: 10.1007/s00405-022-07700-4 -
Development, Growth & Differentiation May 2020In mammals, odorants induce various behavioral responses that are critical to the survival of the individual and species. Binding signals of odorants to odorant... (Review)
Review
In mammals, odorants induce various behavioral responses that are critical to the survival of the individual and species. Binding signals of odorants to odorant receptors (ORs) expressed in the olfactory epithelia are converted to an odor map, a pattern of activated glomeruli, in the olfactory bulb (OB). This topographic map is used to identify odorants for memory-based learned decisions. In the embryo, a coarse olfactory map is generated in the OB by a combination of dorsal-ventral and anterior-posterior targeting of olfactory sensory neurons (OSNs), using specific sets of axon-guidance molecules. During the process of OSN projection, odor signals are sorted into distinct odor qualities in separate functional domains in the OB. Odor information is then conveyed by the projection neurons, mitral/tufted cells, to various regions in the olfactory cortex, particularly to the amygdala for innate olfactory decisions. Although the basic architecture of hard-wired circuits is generated by a genetic program, innate olfactory responses are modified by neonatal odor experience in an activity-dependent manner. Stimulus-driven OR activity promotes post-synaptic events and dendrite selection in the responding glomeruli making them larger. As a result, enhanced odor inputs in neonates establish imprinted olfactory memory that induces attractive responses in adults, even when the odor quality is innately aversive. In this paper, I will provide an overview of the recent progress made in the olfactory circuit formation in mice.
Topics: Animals; Mice; Odorants; Olfactory Bulb; Olfactory Receptor Neurons; Receptors, Odorant
PubMed: 32112394
DOI: 10.1111/dgd.12657 -
Brain Pathology (Zurich, Switzerland) May 2022Several degenerative brain disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are characterized by the simultaneous...
Several degenerative brain disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are characterized by the simultaneous appearance of amyloid-β (Aβ) and α-synuclein (α-syn) pathologies and symptoms that are similar, making it difficult to differentiate between these diseases. Until now, an accurate diagnosis can only be made by postmortem analysis. Furthermore, the role of α-syn in Aβ aggregation and the arising characteristic olfactory impairments observed during the progression of these diseases is still not well understood. Therefore, we assessed Aβ load in olfactory bulbs of APP-transgenic mice expressing APP695 and PSEN1 under the control of the neuron-specific Thy-1 promoter (referred to here as APPPS1) and APPPS1 mice co-expressing SNCA (referred to here as APPPS1 × [A30P]aSYN). Furthermore, the olfactory capacity of these mice was evaluated in the buried food and olfactory avoidance test. Our results demonstrate an age-dependent increase in Aβ load in the olfactory bulb of APP-transgenic mice that go along with exacerbated olfactory performance. Our study provides clear evidence that the presence of α-syn significantly diminished the endogenous and seed-induced Aβ deposits and significantly ameliorated olfactory dysfunction in APPPS1 × [A30P]aSYN mice.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Disease Models, Animal; Mice; Mice, Transgenic; Olfactory Bulb; Synucleinopathies; alpha-Synuclein
PubMed: 34713522
DOI: 10.1111/bpa.13032 -
The Journal of Neuroscience : the... May 2022Odors are transported by turbulent air currents, creating complex temporal fluctuations in odor concentration that provide a potentially informative stimulus dimension....
Odors are transported by turbulent air currents, creating complex temporal fluctuations in odor concentration that provide a potentially informative stimulus dimension. We have shown that mice are able to discriminate odor stimuli based on their temporal structure, indicating that information contained in the temporal structure of odor plumes can be extracted by the mouse olfactory system. Here, using extracellular and intracellular electrophysiological recordings, we show that mitral cells (MCs) and tufted cells (TCs) of the male C57BL/6 mouse olfactory bulb can encode the dominant temporal frequencies present in odor stimuli up to at least 20 Hz. A substantial population of cell-odor pairs showed significant coupling of their subthreshold membrane potential with the odor stimulus at both 2 Hz (29/70) and the suprasniff frequency 20 Hz (24/70). Furthermore, mitral/tufted cells (M/TCs) show differential coupling of their membrane potential to odor concentration fluctuations with tufted cells coupling more strongly for the 20 Hz stimulation. Frequency coupling was always observed to be invariant to odor identity, and M/TCs that coupled well to a mixture also coupled to at least one of the components of the mixture. Interestingly, pharmacological blocking of the inhibitory circuitry strongly modulated frequency coupling of cell-odor pairs at both 2 Hz (10/15) and 20 Hz (9/15). These results provide insight into how both cellular and circuit properties contribute to the encoding of temporal odor features in the mouse olfactory bulb. Odors in the natural environment have a strong temporal structure that can be extracted and used by mice in their behavior. Here, using extracellular and intracellular electrophysiological techniques, we show that the projection neurons in the olfactory bulb can encode and couple to the dominant frequency present in an odor stimulus. Furthermore, frequency coupling was observed to be differential between mitral and tufted cells and was odor invariant but strongly modulated by local inhibitory circuits. In summary, this study provides insight into how both cellular and circuit properties modulate encoding of odor temporal features in the mouse olfactory bulb.
Topics: Animals; Interneurons; Male; Mice; Mice, Inbred C57BL; Neurons; Odorants; Olfactory Bulb; Smell
PubMed: 35440491
DOI: 10.1523/JNEUROSCI.1422-21.2022 -
Neuroradiology Jan 2023The neurotropism of SARS-CoV-2 and the consequential damage to the olfactory system have been proposed as one of the possible underlying causes of olfactory dysfunction... (Meta-Analysis)
Meta-Analysis
PURPOSE
The neurotropism of SARS-CoV-2 and the consequential damage to the olfactory system have been proposed as one of the possible underlying causes of olfactory dysfunction in COVID-19. We aimed to aggregate the results of the studies which reported imaging of the olfactory system of patients with COVID-19 versus controls.
METHODS
PubMed and EMBASE were searched to identify relevant literature reporting the structural imaging characteristics of the olfactory bulb (OB), olfactory cleft, olfactory sulcus (OS), or olfactory tract in COVID-19 patients. Hedge's g and weighted mean difference were used as a measure of effect size. Quality assessment, subgroup analyses, meta-regression, and sensitivity analysis were also conducted.
RESULTS
Ten studies were included in the qualitative synthesis, out of which seven studies with 183 cases with COVID-19 and 308 controls without COVID-19 were enrolled in the quantitative synthesis. No significant differences were detected in analyses of right OB volume and left OB volume. Likewise, right OS depth and left OS depth were also not significantly different in COVID-19 cases compared to non-COVID-19 controls. Also, we performed subgroup analysis, meta-regression, and sensitivity analysis to investigate the potential effect of confounding moderators.
CONCLUSION
The findings of this review did not confirm alterations in structural imaging of the olfactory system, including OB volume and OS depth by Covid-19 which is consistent with the results of recent histopathological evaluations.
Topics: Humans; Olfaction Disorders; COVID-19; SARS-CoV-2; Magnetic Resonance Imaging; Olfactory Bulb
PubMed: 35843987
DOI: 10.1007/s00234-022-03014-8 -
International Journal of Molecular... Dec 2021Particulate matter (PM) is an environmental hazard that is associated with various human health risks. The olfactory system is directly exposed to PM; therefore, the...
Particulate matter (PM) is an environmental hazard that is associated with various human health risks. The olfactory system is directly exposed to PM; therefore, the influence of PM exposure on olfactory function must be investigated. In this study, we propose a zebrafish olfactory model to evaluate the effects of exposure to diesel particulate matter (DPM), which was labeled Korean diesel particulate matter (KDP20). KDP20 comprises heavy metals and polycyclic aromatic hydrocarbons (PAHs). KDP20 exposed olfactory organs exhibited reduced cilia and damaged epithelium. Olfactory dysfunction was confirmed using an odor-mediated behavior test. Furthermore, the olfactory damage was analyzed using Alcian blue and anti-calretinin staining. KDP20 exposed olfactory organs exhibited histological damages, such as increased goblet cells, decreased cell density, and calretinin level. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that PAHs exposure related genes ( and ) were upregulated. Reactive oxidation stress (ROS) () and inflammation () related genes were upregulated. Furthermore, olfactory sensory neuron (OSN) related genes ( and ) were downregulated. In conclusion, KDP20 exposure induced dysfunction of the olfactory system. Additionally, the zebrafish olfactory system exhibited a regenerative capacity with recovery conditions. Thus, this model may be used in future investigating PM-related diseases.
Topics: Aging; Animals; Behavior, Animal; Calbindin 2; Dynamic Light Scattering; Odorants; Olfactory Bulb; Particle Size; Particulate Matter; Spectrometry, X-Ray Emission; Survival Analysis; Vehicle Emissions; Zebrafish
PubMed: 35008830
DOI: 10.3390/ijms23010407 -
Pediatric Radiology Sep 2019We describe association of olfactory bulb and olfactory tract abnormalities in a child with acrocallosal syndrome caused by kinesin family membrane 7 (KIF7) mutation in...
We describe association of olfactory bulb and olfactory tract abnormalities in a child with acrocallosal syndrome caused by kinesin family membrane 7 (KIF7) mutation in sonic hedgehog pathway. The child also had fontanellar bone in the anterior fontanelle, short sagittal suture, sagittal synostosis, hippocampal malrotation and Joubert malformation. Fontanellar bone has been described in GLI3 mutation and mutant mice models but has not been reported in KIF7 mutation. We briefly review the role of sonic hedgehog pathway and its components KIF7 and GLI3 in forebrain and olfactory system development and also describe olfactory system abnormality in a child with GLI3 mutation.
Topics: Abnormalities, Multiple; Acrocallosal Syndrome; Acrocephalosyndactylia; Brain; Child, Preschool; Female; Humans; Infant; Magnetic Resonance Imaging; Olfactory Bulb; Tomography, X-Ray Computed
PubMed: 31399769
DOI: 10.1007/s00247-019-04480-8