Search Results (185)

Background/Objectives: Aging is one of the greatest risk factors for neurodegenerative diseases such as Alzheimer’s disease (AD). As the disease progresses, neural loss in brain regions, such as the olfactory cortex (OC), i.e., a set of areas including the mediotemporal and orbitofrontal regions, may lead to dysfunction in the sense of smell and affect other brain regions that relate to the olfactory cortex by either afferent or efferent projections. Methods: The objective of this study was to assess sex-related differences in olfactory cortex volume using magnetic resonance imaging in individuals with mild cognitive impairment, probable dementia of the AD type and in healthy older adults, using the Mini-Mental Statement Examination score, years of education, and total intracranial volume as correction factors. Results: Atrophy of the olfactory cortex was observed in patients of both sexes with probable AD dementia. However, at the MCI stage, significant volumetric loss in the OC was detected in females only but not in males. Conclusions: This finding indicates greater pathological effects in this region in females at an earlier disease stage than in males. This study suggests that OC volume loss occurs differently between the sexes in older adults, with volumetric loss being greater in females. Full article

Background/Objectives: Primary Ciliary Dyskinesia (PCD) is a rare genetic condition characterized by compromised mucociliary clearance and chronic respiratory manifestations. Anosmia, or the loss of smell, is a lesser-known but clinically relevant symptom that can significantly impact patient safety, nutritional status, and the overall quality of life. The RSPH4A (c.921+3_921+6delAAGT) founder mutation is highly prevalent among Puerto Rican individuals with PCD and may carry distinct phenotypic implications. This study aimed to evaluate olfactory function in Puerto Rican PCD patients with this mutation using the Brief Smell Identification Test (BSIT^®) and to assess associations with age and sex. Methods: We conducted a case–control study involving 30 participants, including 15 PCD patients with genetically confirmed RSPH4A mutations and 15 age- and sex-matched healthy controls. All participants completed the BSIT, and BSIT scores were compared by diagnosis, sex, and age. Results: PCD patients had significantly lower BSIT scores than controls (p = 0.0015). When stratified by sex, both male (p = 0.0289) and female (p = 0.0178) PCD patients demonstrated significantly lower BSIT scores compared to their respective healthy counterparts. Regression analysis showed a significant inverse correlation between age and BSIT score in the PCD group (r² = 0.2873; p = 0.0395), while no such relationship was observed in controls (r² = 0.0096; p = 0.7283). Among PCD patients, age-related decline in olfactory function was more pronounced in females (r² = 0.71; p = 0.005) than in males (r² = 0.31; p = 0.25). Conclusions: These findings demonstrate that the RSPH4A founder mutation is associated with measurable olfactory impairment in PCD patients, particularly in females and with advancing age. The routine assessment of olfactory function should be considered in the clinical evaluation of patients with PCD, as anosmia may represent a key phenotypic feature and contribute to disease burden. Full article

Olfactory dysfunction is a clinical marker of prodromal Parkinson’s disease (PD), yet the underlying mechanisms remain unclear. To explore this relationship, we developed a zebrafish model that recapitulates the olfactory impairment observed in prodromal PD without affecting motor function. We used zebrafish due to their olfactory system’s similarity to mammals and their unique nervous system regenerative capacity. By injecting 6-hydroxydopamine (6-OHDA) into the dorsal telencephalic ventricle, we observed a significant loss of dopaminergic (DA) periglomerular neurons in the olfactory bulb (OB) and retrograde degeneration of olfactory sensory neurons (OSNs) in the olfactory epithelium (OE). These alterations impaired olfactory responses to cadaverine, an aversive odorant, while responses to alanine remained intact. 6-OHDA also triggered robust neuroinflammatory responses. By 7 days post-injection, dopaminergic synapses in the OB were remodeled, OSNs in the OE appeared recovered, and neuroinflammation subsided, leading to full recovery of olfactory responses to cadaverine. These findings highlight the remarkable neuroplasticity of zebrafish and suggest that this model of olfactory dysfunction associated with dopaminergic loss could provide valuable insights into some features of early PD pathology. Understanding the interplay between dopaminergic loss and olfactory dysfunction in a highly regenerative vertebrate may inform therapeutic strategies for individuals suffering from olfactory loss. Full article

Background: Parkinson’s disease (PD) is characterized by early-onset olfactory dysfunction preceding motor symptoms, yet its mechanisms remain elusive. Based on the studies on microbiota-gut-brain axis, the microbiota–nose–brain axis might be involved in the pathogenesis of PD. However relative studies are rare. Methods: By consecutive 14-days intranasally transplanting bacteria, we established mice models exhibiting nasal microbiota dysbiosis (NMD), including animal group received intranasal drops of fecal bacterial suspension from normal mice (NB group) and animal group received intranasal drops of fecal bacterial suspension from PD mice (PB group), with animals that only received anesthesia used as the control group. Then we analyzed the nasal microbiota composition via 16S rRNA sequencing, evaluated the olfactory and motor functions through behavioral experiments, including buried food test, open field test, pole descent test, and traction test. The neuropathology in olfactory-related and PD-related brain regions, including olfactory bulb, pyriform cortex, hippocampus, substantia nigra and striatum, was also detected by western blotting, immunofluorescence and immunohistochemical experiments using the antibodies of NeuN, TH and GFAP. Results: 16S rRNA sequencing revealed that PB mice were primarily characterized by an increase in bacteria associated with inflammation and PD. Behavioral assessments revealed that mice with NMD demonstrated impairments in the buried food test and pole descent test, indicative of olfactory and motor dysfunction. By detecting NeuN and GFAP expression, we identified neuronal loss and astrocytes activation in olfactory-related brain regions and adjacent structures, including the olfactory bulb, pyriform cortex, hippocampus, substantia nigra and striatum of both NMD groups, which may contribute to the observed functional disorders. Notably, animals exposed to PD-derived bacteria exhibited more pronounced changes in nasal bacteria, with more severe neuropathology. Conclusions: We present evidence supporting the microbiota–nose–brain axis, and the NMD-induced astrocyte activation and neurodegenerative pathology along the olfactory pathway may serve as a link between nose and brain. Full article

Background/Objectives: Autism is a complex neurodevelopmental disorder characterized by restricted behaviors and impaired social and communication skills. The exact cause of autism remains unknown. One promising animal model for studying autism is the valproic acid rat model. Due to a 1 to 4 bias for males in autism occurrence, most animal model studies investigate only males and neglect females. However, female autism often appears different from that observed in males. Females are said to be less regularly diagnosed because they can “mask” their symptoms. Female autism is as necessary to investigate as male autism. Methods: Fertile adult female Sprague-Dawley rats were impregnated and injected with valproic acid on gestational day 13. Male and female offspring were subjected to behavioral tests to investigate autistic symptoms. Tests included novel object recognition, balance-beam, Y-maze, hole-board, three-chamber, marble burying, olfactory, light/dark and hot plate tests. Results: The tests revealed that VPA-exposed rats had increased anxiety-like behaviors, hyperactivity, and impaired non-verbal communication. However, they did not display repetitive behaviors or cognitive impairments. Notably, male and female rats showed different autism-like traits, with both showing hyperactivity, and males (but not females) additionally showing impaired sociability and increased anxiety. Conclusions: The findings suggest that prenatal exposure to VPA induces autism-like behaviors in both male and female Sprague-Dawley rat offspring. However, males appear more impacted by VPA exposure as evinced by their display of more autism-like symptoms relative to females. This study provides support for including both sexes in all studies modelling autism, as outcomes are seemingly impacted by the sex being observed. Full article

Air pollution plays a key role in sleep disorders and neurodegeneration. Alzheimer’s disease (AD), Parkinson’s disease (PD), and/or transactive response DNA-binding protein TDP-43 neuropathology have been documented in children and young adult forensic autopsies in the metropolitan area of Mexico City (MMC), along with sleep disorders, cognitive deficits, and MRI brain atrophy in seemingly healthy young populations. Ultrafine particulate matter (UFPM) and industrial nanoparticles (NPs) reach urbanites’ brains through nasal/olfactory, lung, gastrointestinal tract, and placental barriers. We documented Fe UFPM/NPs in neurovascular units, as well as lateral hypothalamic nucleus orexinergic neurons, thalamus, medullary, pontine, and mesencephalic reticular formation, and in pinealocytes. We quantified ferromagnetic materials in sleep and arousal brain hubs and examined their motion behavior to low magnetic fields in MMC brain autopsy samples from nine children and 25 adults with AD, PD, and TDP-43 neuropathology. Saturated isothermal remanent magnetization curves at 50–300 mT were associated with UFPM/NP accumulation in sleep/awake hubs and their motion associated with 30–50 µT (DC magnetic fields) exposure. Brain samples exposed to anthropogenic PM pollution were found to be sensitive to low magnetic fields, with motion behaviors that were potentially linked to the early development and progression of fatal neurodegenerative diseases and sleep disorders. Single-domain magnetic UFPM/NPs in the orexin system, as well as arousal, sleep, and autonomic regions, are key to neurodegeneration, behavioral and cognitive impairment, and sleep disorders. We need to identify children at higher risk and monitor environmental UFPM and NP emissions and exposures to magnetic fields. Ubiquitous ferrimagnetic particles and low magnetic field exposures are a threat to global brain health. Full article

Neurological symptoms such as impaired smell and taste have been recognized as hallmark manifestations of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. This study investigates and quantifies microstructural changes in the white matter of the olfactory bulb and taste-related brain regions (frontal operculum, insular cortex and parietal operculum) using diffusion-weighted magnetic resonance imaging (DW-MRI). Apparent diffusion coefficient (ADC) values were measured in patients with confirmed coronavirus disease of 2019 (COVID-19) at the onset of anosmia and ageusia (24 patients, scanned between March and December 2020), 1 month post-infection (20 subjects) and 36 months post-infection (20 participants). ADC values were analyzed over time and compared to normal white matter ADC ranges (calculated retrospectively from 979 pre-pandemic patients) and to those from patients infected with the 2024 strain of SARS-CoV-2 (27 patients). The results revealed significantly elevated ADC values in the white matter of the targeted brain regions, with a peak at the time of infection, followed by a decline 1 month post-infection, and a return to near-normal levels 3 years later. In contrast, the 2024 COVID-19 variant demonstrated reduced virus-related alterations in brain microstructure compared to the 2020 strain. These findings highlight the potential of DWI as a non-invasive tool for elucidating the molecular mechanisms underlying olfactory and taste dysfunction in COVID-19 patients. Full article

Background/Objectives: Olfactory decline is common in normal aging and frequent in neurodegenerative diseases such as Alzheimer’s disease (AD). Therefore, it has been suggested as a marker for the Mild Cognitive Impairment (MCI) progression to AD. Although suggested, the relationship between olfactory deficits and cerebral atrophy in MCI conversion to AD is still debated. This study aims at investigating the olfaction-related morphological and behavioural alterations in MCI in order to understand whether they can predict the progression to AD. Methods: Twenty-seven MCI patients and thirty-five healthy controls (HCs) took part in the study, with follow-up showing conversion to AD in thirteen patients (converter-MCI, cMCI). The Burgarth Sniffin’ Sticks Tests (threshold—TT, discrimination—DT, identification—IT) assessed the olfactory capacities. The Voxel-Based Morphometry (VBM) analysis investigated the atrophic patterns. Results: The Receiving Operating Characteristics analyses demonstrated that DT and IT could distinguish HC from MCI (DT Area Under Curve—AUC = 0.8; IT AUC = 0.8), as well as cMCI from sMCI (stable) patients (DT AUC = 0.7; IT AUC = 0.6), similarly to memory and executive functions tests. Olfactory performance positively correlated with memory tests in sMCI (all rhos ≥ 0.8, all ps < 0.01), whereas it positively correlated with executive functions in cMCI (all rhos ≥ 0.6, all ps < 0.05). VBM results revealed distinct atrophic patterns in cMCI, especially in the olfactory cortex, that were already present at the MCI diagnosis, before AD conversion. A larger volume of the olfactory cortex was associated with better memory and executive functions. Conclusions: Quantitative olfactory and morphological patterns represent non-invasive, predictive biomarkers of the MCI progression to AD; thus, their assessments at MCI onset allows earlier interventions for MCI patients. Full article

An abnormal accumulation of misfolded proteins is a common feature shared by most neurodegenerative disorders. Olfactory dysfunction (OD) is common in the elderly population and is present in 90% of patients with Alzheimer’s or Parkinson’s disease, usually preceding the cognitive and motor symptoms onset by several years. Early Aβ, tau, and α-synuclein protein aggregates deposit in brain structures involved in odor processing (olfactory bulb and tract, piriform cortex, amygdala, entorhinal cortex, and hippocampus) and seem to underly OD. The glymphatic system is a glial-associated fluid transport system that facilitates the movement of brain fluids and removes brain waste during specific sleep stages. Notably, the glymphatic system became less functional in aging and it is impaired in several conditions, including neurodegenerative diseases. As the nasal pathway has been recently described as the main outflow exit of cerebrospinal fluid and solutes, we hypothesized that OD may indeed be a clinical marker of early glymphatic dysfunction through abnormal accumulation of pathological proteins in olfactory structures. This effect may be more pronounced in peri- and postmenopausal women due to the well-documented impact of estrogen loss on the locus coeruleus, which may disrupt multiple mechanisms involved in glymphatic clearance. If this hypothesis is confirmed, olfactory dysfunction might be considered as a clinical proxy of glymphatic failure in neurodegenerative diseases. Full article

Neurological and olfactory disturbances are increasingly recognized as potential complications of general anesthesia, particularly in vulnerable populations, such as the elderly, children, and individuals with comorbidities. Recent studies have highlighted the need for tailored anesthetic approaches in these high-risk groups to mitigate potential long-term effects. These disturbances, including postoperative cognitive dysfunction, delirium, and olfactory deficits, often arise from shared pathophysiological mechanisms, such as neuroinflammation, oxidative stress, and disruptions in cerebral perfusion. The olfactory system is particularly susceptible to anesthesia-induced neurotoxicity given its proximity to central nervous system structures and its role in sensory and cognitive processing. Furthermore, the unique regenerative capacity of olfactory neurons may be compromised by prolonged or repeated exposure to anesthetic agents, potentially leading to long-term olfactory dysfunction. Risk factors, such as advanced age, neurodegenerative diseases, diabetes, cardiovascular conditions, genetic predispositions, and the type and duration of anesthesia exposure, further exacerbate these complications. Preventive strategies, including comprehensive preoperative risk assessment, personalized anesthetic protocols based on genetic and physiological profiles, and proactive postoperative care with early intervention programs, are critical for reducing impairments and improving long-term patient outcomes. Emerging evidence highlights the potential role of neuroprotective agents, such as antioxidants and anti-inflammatory therapies, in mitigating the effects of anesthesia-induced neurotoxicity. Longitudinal studies are needed to evaluate the long-term effects of anesthesia on cognitive and sensory health, particularly in high-risk populations. These studies should incorporate advanced neuroimaging techniques and biomarker analysis to elucidate the underlying mechanisms of anesthesia-induced neurological and olfactory disturbances. This narrative review provides a comprehensive overview of the mechanisms, risk factors, and preventive strategies for neurological and olfactory disturbances after general anesthesia and highlights future directions for research to improve patient outcomes. We conducted a comprehensive literature search using databases, such as PubMed and Scopus, to identify relevant studies. Full article

The hierarchical perspective on senses has relegated smell to the lowest rank in Western culture while granting vision superiority. Studies show that olfactory impairments, like vision and hearing impairments, reduce quality of life. Our study examines the perceived value of smell in a student population in comparison to hearing and vision, hypothesizing differences based on previous loss of smell (≥2 weeks) and gender. University students were enlisted in a survey comparing smell to vision, hearing, and forfeiting the senses for various commodities (phone, EUR 10,000, hair, and social media). A total of 200 participants completed the survey, with 52 reporting previous loss of smell and 148 reporting no history of smell loss. Overall, smell was the most frequently forfeited sense. While the sacrifice of hearing and vision remained consistent across various commodities, smell was notably forfeited more for certain items. When comparing groups with and without previous loss of smell, no significant differences were observed in forfeiting the senses across various commodities, except for hair. However, it is noteworthy that smell was forfeited more often for all commodities when considering percentages. Furthermore, females exhibited a greater willingness to sacrifice their sense of smell for USD 10,000 and hair. Smell is valued the lowest among the three senses when asked directly and compared to various commodities. There were no significant differences in its perceived value between those with and without previous loss of smell. Furthermore, females tend to value their sense of smell less than males, according to the surveyed commodities. Full article

Parkinson’s disease (PD) is a neurological disorder characterized by heterogeneous symptomatology, in which the classical motor features of Parkinsonism are associated with clinically significant non-motor symptoms. Olfactory alteration, as a manifestation of PD’s premotor or prodromal phase, is well known. These impairments can lead to malnutrition, decreased appetite, and depression, thereby worsening patients’ quality of life. However, only a few studies clarify the mechanisms, characteristics, and clinical diagnostic and therapeutic implications of impaired taste perception. Moreover, unlike most motor features of PD, non-motor symptoms often have limited treatment options or responses. The purpose of this review is to collate and describe all relevant studies on taste and smell alterations in patients with PD and how these alterations could affect nutritional status. Our search aimed to identify English-language research articles and reviews published in peer-reviewed journals over the past two decades (2004–2024), while also including older foundational studies when relevant. Several studies show that hyposmia in PD worsens over time, potentially linked to structural changes in the brain’s basal ganglia and piriform cortex. Severe hyposmia is also associated with a higher risk of dementia in PD patients and can negatively influence quality of life, affecting social interactions and nutrition. Regarding taste perception, recent studies have suggested that hypogeusia may occur even in the prodromal stage of PD, such as in patients with REM sleep disorder, although the exact mechanisms remain unclear. Additionally, research has explored the role of bitter taste receptors and their possible involvement in inflammation and α-synuclein misfolding, suggesting a link between taste dysfunction and immune system changes in PD. Attention was then focused on the gut microbiota’s link to the central nervous system and its contribution to gustatory dysfunctions, as well as how the nasal microbiome influences PD progression by altering the olfactory system. Nowadays, the primary role of a correct diet in the overall treatment of PD patients is becoming increasingly important for practitioners. Diet should be included among the available aids to counteract some aspects of the pathology itself. For all these reasons, it is also crucial to determine whether these chemosensory impairments could serve as disease markers, helping to better understand the underlying mechanisms of the disease. Full article

Objectives: Evidence for the usefulness of biomarkers that aid in diagnosis, assessment of severity, and prediction of prognosis in patients with long COVID is limited. The aim of this study was to clarify the characteristics of brain natriuretic peptide (BNP) in long COVID. Methods: We conducted a retrospective observational study of patients who visited the COVID-19 aftercare outpatient clinic at Okayama University Hospital from February 2021 to April 2024. Results: A total of 428 patients were enrolled in this study, and the patients were divided into a group with normal BNP (n = 314, ≤18.4 pg/mL) and a group with increased BNP (n = 114, >18.4 pg/mL). The long COVID group with increased BNP had a higher proportion of females (44.3% vs. 73.7%, p < 0.01) and an older median age (38 vs. 51 years, p < 0.01). Fatigue and brain fog were commonly manifested in both groups, while dyspnea was a more frequent complaint in the group with increased BNP. Various symptoms including fatigue, palpitations, and taste and/or olfactory disorders were associated with elevated BNP (23 to 24 pg/mL). Memory impairment was also linked to higher BNP (OR: 2.36, p = 0.05). In long COVID patients, plasma BNP elevation appears to be more pronounced in females and is often related to cardiogenic factors, in which inflammatory responses are also involved. Conclusions: Plasma BNP measurement may be useful for evaluating the severity of long COVID, especially in female patients and those with respiratory symptoms and/or memory impairment. Full article

Anthropic activities have significantly elevated cadmium levels, making it a significant stressor in aquatic ecosystems. Present in high concentrations across water bodies, cadmium is known to bioaccumulate and biomagnify throughout the food chain. While the toxic effects of cadmium on the organs and tissues of aquatic species are well-documented, little is known about its impact on sensory systems crucial for survival. Consequently, this study investigated the impact of short-term exposure (96 h) to 25 µM cadmium chloride on the olfactory system of adult zebrafish. The research aimed to assess structural and functional changes in the zebrafish’s olfactory lamellae, providing a deeper understanding of how cadmium affects the sense of smell in this aquatic species. After exposure, cyto-anatomical alterations in the lamellae were analysed using light microscopy and immunocytochemistry. They revealed severe lamellar edema, epithelial thickening, and an increased number of apoptotic and crypt cells. Rodlet and goblet cells also increased by 3.5- and 2.5-fold, respectively, compared to control lamellae, and collagen density in the lamina propria increased 1.7-fold. Cadmium upregulated metallothioneins and increased the number of PCNA-positive cells. The olfactory function was assessed through a behavioural odour recognition test, followed by a recovery phase in which zebrafish exposed to cadmium were placed in clean water for six days. The exposed fish performed poorly, failing to reach food in five consecutive trials. However, lamellar damage was reduced after the recovery period, and their performance improved, becoming comparable to the control group. These results suggest that cadmium disrupts the sense of smell, and that recovery is possible after short-term exposure. This evidence sheds light on aspects of animal survival that are often overlooked when assessing environmental pollution. Full article

Background/Objectives: This study evaluated changes in circadian clock genes and mitochondrial function in a lead (Pb)-induced toxicity model of an olfactory epithelial cell line. Methods: The DBC1.2 olfactory dark basal cell line was used. Dexamethasone shock was used to reset the circadian clock 24 h (Group 1) and 36 h (Group 2) after seeding. Then, 60 h after seeding, the cells were treated with or without Pb (II) nitrate in HEPES buffer for 1 h. Mitochondrial function and cell viability were evaluated 84 h after seeding. Results: Mitochondrial function under Pb exposure was significantly impaired in Group 1 compared with Group 2. Cell numbers and viability did not significantly differ between groups. The mitochondrial membrane potential was significantly higher in Group 1 than Group 2, both without and with Pb exposure. Conclusions: The circadian rhythm can alter the sensitivity to Pb-induced toxicity and mitochondrial damage in olfactory cells. Full article