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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 -
Journal of Bioenergetics and... Feb 2019Experiences, such as sensory learning, are known to induce plasticity in mammalian sensory systems. In recent years aversive olfactory learning-induced plasticity has... (Review)
Review
Experiences, such as sensory learning, are known to induce plasticity in mammalian sensory systems. In recent years aversive olfactory learning-induced plasticity has been identified at all stages of the adult olfactory pathway; however, the underlying mechanisms have yet to be identified. Much of the work regarding mechanisms of olfactory associative learning comes from neonates, a time point before which the brain or olfactory system is fully developed. In addition, pups and adults often express different behavioral outcomes when subjected to the same olfactory aversive conditioning paradigm, making it difficult to directly attribute pup mechanisms of plasticity to adults. Despite the differences, there is evidence of similarities between pups and adults in terms of learning-induced changes in the olfactory system, suggesting at least some conserved mechanisms. Identifying these conserved mechanisms of plasticity would dramatically increase our understanding of how the brain is able to alter encoding and consolidation of salient olfactory information even at the earliest stages following aversive learning. The focus of this review is to systematically examine literature regarding olfactory associative learning across developmental stages and search for similarities in order to build testable hypotheses that will inform future studies of aversive learning-induced sensory plasticity in adults.
Topics: Animals; Humans; Learning; Mammals; Neuronal Plasticity; Olfactory Bulb; Smell
PubMed: 30171506
DOI: 10.1007/s10863-018-9770-z -
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 -
Experimental Gerontology Aug 2017In the anterior forebrain, along the lateral wall of the lateral ventricles, a neurogenic stem cell niche is found in a region referred to as the... (Review)
Review
In the anterior forebrain, along the lateral wall of the lateral ventricles, a neurogenic stem cell niche is found in a region referred to as the ventricular-subventricular zone (V-SVZ). In rodents, robust V-SVZ neurogenesis provides new neurons to the olfactory bulb throughout adulthood; however, with increasing age stem cell numbers are reduced and neurogenic capacity is significantly diminished, but new olfactory bulb neurons continue to be produced even in old age. Humans, in contrast, show little to no new neurogenesis after two years of age and whether V-SVZ neural stem cells persist in the adult human brain remains unclear. Here, we review functional and organizational differences in the V-SVZ stem cell niche of mice and humans, and examine how aging affects the V-SVZ niche and its associated functions.
Topics: Age Factors; Aging; Animals; Cell Movement; Cell Proliferation; Humans; Lateral Ventricles; Neural Stem Cells; Neurogenesis; Olfactory Bulb; Prosencephalon; Species Specificity; Stem Cell Niche
PubMed: 27867091
DOI: 10.1016/j.exger.2016.11.007 -
Scientific Reports Jun 2024Despite its high prevalence, the determinants of smelling impairment in COVID-19 remain not fully understood. In this work, we aimed to examine the association between...
Despite its high prevalence, the determinants of smelling impairment in COVID-19 remain not fully understood. In this work, we aimed to examine the association between olfactory bulb volume and the clinical trajectory of COVID-19-related smelling impairment in a large-scale magnetic resonance imaging (MRI) analysis. Data of non-vaccinated COVID-19 convalescents recruited within the framework of the prospective Hamburg City Health Study COVID Program between March and December 2020 were analyzed. At baseline, 233 participants underwent MRI and neuropsychological testing as well as a structured questionnaire for olfactory function. Between March and April 2022, olfactory function was assessed at follow-up including quantitative olfactometric testing with Sniffin' Sticks. This study included 233 individuals recovered from mainly mild to moderate SARS-CoV-2 infections. Longitudinal assessment demonstrated a declining prevalence of self-reported olfactory dysfunction from 67.1% at acute infection, 21.0% at baseline examination and 17.5% at follow-up. Participants with post-acute self-reported olfactory dysfunction had a significantly lower olfactory bulb volume at baseline than normally smelling individuals. Olfactory bulb volume at baseline predicted olfactometric scores at follow-up. Performance in neuropsychological testing was not significantly associated with the olfactory bulb volume. Our work demonstrates an association of long-term self-reported smelling dysfunction and olfactory bulb integrity in a sample of individuals recovered from mainly mild to moderate COVID-19. Collectively, our results highlight olfactory bulb volume as a surrogate marker that may inform diagnosis and guide rehabilitation strategies in COVID-19.
Topics: Humans; Olfactory Bulb; COVID-19; Male; Female; Middle Aged; Olfaction Disorders; Adult; Magnetic Resonance Imaging; SARS-CoV-2; Aged; Prospective Studies; Neuropsychological Tests; Smell
PubMed: 38862636
DOI: 10.1038/s41598-024-64367-z -
Cell Transplantation Jun 2018Olfactory ensheathing cells (OECs) are glia reported to sustain the continuous axon extension and successful topographic targeting of the olfactory receptor neurons... (Review)
Review
Olfactory ensheathing cells (OECs) are glia reported to sustain the continuous axon extension and successful topographic targeting of the olfactory receptor neurons responsible for the sense of smell (olfaction). Due to this distinctive property, OECs have been trialed in human cell transplant therapies to assist in the repair of central nervous system injuries, particularly those of the spinal cord. Though many studies have reported neurological improvement, the therapy remains inconsistent and requires further improvement. Much of this variability stems from differing olfactory cell populations prior to transplantation into the injury site. While some studies have used purified cells, others have used unpurified transplants. Although both preparations have merits and faults, the latter increases the variability between transplants received by recipients. Without a robust purification procedure in OEC transplantation therapies, the full potential of OECs for spinal cord injury may not be realised.
Topics: Animals; Cell Separation; Cell Transplantation; Humans; Nerve Regeneration; Neuroglia; Olfactory Bulb; Spinal Cord; Spinal Cord Injuries
PubMed: 29882418
DOI: 10.1177/0963689718779353 -
Cerebral Cortex (New York, N.Y. : 1991) Feb 2022The olfactory bulb (OB) delivers sensory information to the piriform cortex (PC) and other components of the olfactory system. OB-PC synapses have been reported to...
The olfactory bulb (OB) delivers sensory information to the piriform cortex (PC) and other components of the olfactory system. OB-PC synapses have been reported to express short-lasting forms of synaptic plasticity, whereas long-term potentiation (LTP) of the anterior PC (aPC) occurs predominantly by activating inputs from the prefrontal cortex. This suggests that brain regions outside the olfactory system may contribute to olfactory information processing and storage. Here, we compared functional magnetic resonance imaging BOLD responses triggered during 20 or 100 Hz stimulation of the OB. We detected BOLD signal increases in the anterior olfactory nucleus (AON), PC and entorhinal cortex, nucleus accumbens, dorsal striatum, ventral diagonal band of Broca, prelimbic-infralimbic cortex (PrL-IL), dorsal medial prefrontal cortex, and basolateral amygdala. Significantly stronger BOLD responses occurred in the PrL-IL, PC, and AON during 100 Hz compared with 20 Hz OB stimulation. LTP in the aPC was concomitantly induced by 100 Hz stimulation. Furthermore, 100 Hz stimulation triggered significant nuclear immediate early gene expression in aPC, AON, and PrL-IL. The involvement of the PrL-IL in this process is consistent with its putative involvement in modulating behavioral responses to odor experience. Furthermore, these results indicate that OB-mediated information storage by the aPC is embedded in a connectome that supports valence evaluation.
Topics: Information Storage and Retrieval; Neuronal Plasticity; Olfactory Bulb; Piriform Cortex; Smell
PubMed: 34379749
DOI: 10.1093/cercor/bhab226 -
Folia Morphologica 2021The aim of this study was to determine the normal reference values for olfactory sulcus depth, olfactory tract length and olfactory bulb volume in the paediatric...
BACKGROUND
The aim of this study was to determine the normal reference values for olfactory sulcus depth, olfactory tract length and olfactory bulb volume in the paediatric population with routine magnetic resonance imaging (MRI) and determine the relationship, if any, between these values and patient sex and age.
MATERIALS AND METHODS
Ninety patients with a median age of 8 years (age range: 3-17 years), consisting of 45 males and 45 females with normal brain MRI scans were evaluated. The patients were divided into three subgroups based on age range, with n = 30 per subgroup; group 1: young children (3-6 years), group 2: children (7-11 years) and group 3: adolescents (12-17 years). In the cranial MRI examination of all groups, the right, left and total olfactory bulb volume values were measured in mm3, the right and left olfactory tract length values and the right and left olfactory sulcus depth values were calculated manually in mm. Demographic data including sex and age were recorded.
RESULTS
There was no significant difference between the age groups in terms of sex. Right-left olfactory sulcus depth; right-left olfactory tract length and right-left total olfactory bulb volume values increased significantly when they are compared in terms of age groups (p < 0.0001, = 0.028; < 0.0001, < 0.0001; < 0.0001, < 0.0001; < 0.0001, respectively). There was no significant difference between right and left olfactory tract length and olfactory bulb volumes in all groups (p = 0.792 and p = 0.478), but the right olfactory sulcus depth was significantly larger than the left (p = 0.003).
CONCLUSIONS
Especially as the age progresses, olfactory tract length and olfactory bulb volume dimensions of olfactory nerve and olfactory sulcus depth should be checked during diagnosis of respective illnesses in paediatric population.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Olfaction Disorders; Olfactory Bulb; Prefrontal Cortex
PubMed: 33084007
DOI: 10.5603/FM.a2020.0125