Atopic dermatitis (AD) is one of the intractable chronic inflammatory diseases and is often accompanied by mental disorders, such as depression. On the other hand, depression has been pointed out to be strongly associated with the onset of anosmia. However, no clinical or basic research report has been conducted on whether olfactory dysfunction develops in patients suffering from AD. Since NC/Tnd mice, a spontaneous AD model, exhibit depressive symptoms, NC/Tnd mice were used to clarify this point. We found that mice with AD completely lost their ability to sniff around after exposed to two different kinds of odors and showed reduced expression of both growth-associated protein-43-positive immature olfactory sensory neurons (OSNs) and olfactory marker protein-positive mature OSNs in the olfactory epithelium. Since elevated levels of IL-4, IL-13, and IL-6 in the peripheral blood were detected in NC/Tnd mice with AD, injection of neutralizing mAb against IL-4Rα or IL-6 improved olfactory function and expression of OSNs. Furthermore, administration with signal inhibitors targeting IL-4Rα and IL-6Rβ resulted in the recovery of olfactory function. The present findings suggest that the activation of the IL-4Rα and IL-6Rβ signal pathways by AD suppresses the expression of OSNs in the olfactory epithelium, leading to the loss of smell.

Despite hyposmia being a dominant non-motor manifestation of Parkinson's disease (PD), its underlying driving mechanisms are poorly defined. The redox protein Thioredoxin-1 (Trx-1) offers neuroprotection against various insults; however, its potential involvement in the neural proliferation in the subventricular zone (SVZ) and neural differentiation in the olfactory bulb (OB) related to MPTP-induced olfactory dysfunction have not been previously established. Our research demonstrates that when Trx-1 is downregulated in the substantia nigra pars compacta (SNpc), MPTP-triggered olfactory deficits are significantly intensified. A key anatomical discovery in our study is the existence of projections from the SNpc to the SVZ. We established that the MPTP-driven death of SNpc dopaminergic (DAergic) neurons correlates with decreased dopamine D1 receptor (D1R) levels in the SVZ, an effect that is magnified by the loss of Trx-1. Alongside D1R reductions, MPTP suppressed a cascade of SVZ signaling molecules (phosphorylated PKA, Wnt3a, β-catenin, Pax6, cyclin D1, and CDK4), with Trx-1 deficiency causing even steeper declines. Furthermore, Trx-1 knockdown hindered the generation of immature neurons and disrupted DAergic neuronal differentiation within the OB. Collectively, our findings suggest that reduced Trx-1 expression in the SNpc may contribute to PD-related olfactory deficits, potentially via inhibiting SVZ neural proliferation, decreasing immature and mature neuron populations, and disrupted differentiation of OB immature neurons. By accelerating MPTP-triggered degeneration of DAergic neurons in the SNpc, Trx-1 downregulation reduces the SVZ of DAergic input. This disruption impairs D1R-mediated the neural proliferation in the SVZ, as well as the maturation and differentiation of immature neurons in OB, ultimately driving the progression of olfactory dysfunction in a PD mouse model.

Persistent symptoms attributed to post-COVID-19 conditions were more frequent among COVID-19-positive individuals, especially smell and taste dysfunction. Vaccination before infection was associated with a lower risk of post-COVID-19 conditions, particularly smell/taste dysfunction, nausea, and hair loss.

Traumatic brain injury (TBI) severity is typically classified using clinical indices that may have limited prognostic value. Objective measures of olfactory function depend on sensory, limbic, and memory networks and may provide a more specific marker of injury-related neural dysfunction. Seventy-nine individuals with TBI (48 mild, 31 moderate-to-severe) and 59 healthy controls completed an olfactory battery, including tests of odor percept identification (OPID9, OPID18), odor discrimination (OD10), and odor memory (POEM) ∼4.04 (4.45) years after their most recent TBI. General linear models examined associations between olfactory outcomes and TBI severity, adjusting for age, age[2], sex, and education. Additional models examined the relationship between loss of consciousness (LOC) and olfactory functioning. The severity of the most recent TBI was significantly associated with all olfactory outcomes, after adjusting for age, sex, and education. Compared with controls, participants with moderate- to-severe TBI showed lower OPID9, OPID18, POEM, and OD10 performance, while participants with mild TBI showed lower OPID18 and POEM performance. LOC was associated specifically with odor memory in these models, as participants with prolonged (> 30min) LOC or LOC of unknown duration had lower POEM scores than those with no LOC. In TBI-only models, LOC remained associated with POEM after adjustment for TBI severity, whereas TBI severity was not associated with POEM after LOC was included. Long term olfactory functioning is sensitive to TBI severity, with generalized impairments across odor identification, discrimination, and odor memory. LOC characteristics appear especially relevant to odor memory, suggesting that olfactory memory may capture injury-related features beyond TBI severity classification alone.

Copper (Cu) is an essential metal involved in neurobiological processes including energy metabolism and neurotransmission, yet dysregulated Cu levels may adversely affect brain health and olfactory performance. Although olfactory dysfunction has primarily been studied in older adults and neurodegenerative disease, adolescence is a critical period of brain maturation during which the olfactory system may be particularly vulnerable. This cross-sectional study examined associations between Cu exposure, olfactory bulb (OB) volume, and olfactory performance in 200 adolescents and young adults (64% female; ages 13-25) from the Public Health Impact of Metals Exposure cohort. Cu concentrations in blood, urine, hair, and saliva were measured using inductively coupled plasma mass spectrometry. T2-weighted magnetic resonance imaging scans estimated left, right, and total OB volumes using a three-stage deep learning pipeline. Olfactory performance was assessed using the Sniffin' Sticks test. Weighted quantile sum regression evaluated associations between a Cu mixture index and OB outcomes, while standard linear regression models assessed individual Cu biomarkers. Models were adjusted for age and sex. A higher Cu index was associated with reduced left (β = -0.72, 95% CI [-1.42, -0.02]), right (β = -0.79, 95% CI [-1.43, -0.15]), and total OB volume (β = -1.55, 95% CI [-2.85, -0.25]), as well as lower odor threshold scores (β = -0.23, 95% CI [-0.42, -0.03]). Individual biomarkers were not independently associated with outcomes. These findings suggest that Cu exposure may adversely affect olfactory neurodevelopment during adolescence and highlight the importance of studying environmental exposures relevant to long-term neurological health.

Parkinson's disease (PD) is characterized by progressive dopaminergic neuron loss and motor and non-motor impairments. Mitochondrial dysfunction and altered post-translational modifications, including SUMOylation, have emerged as key mechanisms in PD pathogenesis. Here, we investigated global SUMOylation changes in in vivo and in vitro PD models induced by MPTP and MPP[+], respectively. Intranasal MPTP administration in rats induced region- and time-dependent changes in Ubc9 and SENP3 across the olfactory bulb, prefrontal cortex, striatum, and hippocampus. In primary cortical neurons, MPP[+] reduced SUMO-2/3 conjugation, Ubc9 and SENP3 levels, along with the mitochondrial fission proteins Drp1 and Mff. Notably, SENP3 showed opposite regulation in vivo and in vitro, highlighting model-specific SUMOylation responses to neurotoxic stress. These findings suggest that context-dependent alterations in SUMOylation and mitochondrial dynamics contribute to PD pathogenesis.

Air pollution, composed of several complex particles, is regarded as one of the major causes of adverse health outcomes, and particulate matter (PM), which occurs primarily as PM10, PM2.5, and PM0.1 according to its aerodynamic diameter, is considered to be the most dangerous fraction. It is known to impair the healthy functioning of organ systems, including the cardiovascular system, respiratory system, gastrointestinal system, and reproductive system. Upon inhalation, the respirable fraction of PM can travel through the olfactory bulb and reach the brain, disrupting the blood-brain barrier (BBB), or act through peripheral responses, thereby causing neuroinflammation and oxidative stress in the brain. PM exposure activates unfolded protein response (UPR) and proapoptotic signals like CHOP and caspase-12, which drive brain cell death. It also impairs oxidative phosphorylation, increases ROS, and initiates mitochondrial permeability transition, which results in neuronal energy failure. Upon entering the system, it compromises the autophagic flux and lysosomal integrity, leading to its accumulation. Although the systemic effects of PM are widely recognized, its capacity to penetrate the central nervous system (CNS) poses a significant biological concern. This review maps how PM alters CNS components, leading to neuroinflammation and ultimately neurotoxicity, and examines the upstream and downstream mechanisms underlying these actions.

Background Despite the high prevalence of smell disorders, there are only a few centres specialising in the evaluation and treatment of patients with smell and taste disorders. While the comprehensive evaluation at centres requires considerable coordination, basic management techniques can be implemented with minimal effort. Summary This manuscript provides guidance on implementing these steps to provide a meaningful workup in patients with smell and taste disorders. Patients can be evaluated using a stepwise process to assess self-reported smell function. Key messages The impact of olfactory dysfunction should be documented using validated, disease-specific quality-of-life questionnaires. Nasal endoscopy is mandatory to rule out sinonasal inflammation, one of the most frequent underlying etiologies of smell disorders. Further comprehensive evaluation must include a thorough patient history and psychophysical tests of odour identification and gustatory function.

Alzheimer's disease (AD) is the most common cause of dementia and major public-health challenge in aging societies worldwide. Accumulating evidence suggests that olfactory and visual deficits can precede overt cognitive symptoms and are closely associated with amyloid-β deposition, pathological tau phosphorylation, and disease progression. Early sensory abnormalities in AD likely arise from converging pathological processes. Among these, chronic neuroinflammation marked by microglial and astrocytic reactivity, inflammasome activation and increased pro-inflammatory mediators might play a pivotal role linking sensory-circuit injury to neurodegeneration. A coherent synthesis of the inflammatory mechanisms underlying early olfactory and visual impairment in AD remains limited, and putative molecular pathways and interventions have not been fully integrated. We aimed to identify AD-related olfactory and visual or retinal abnormalities, combine core inflammatory pathways and their interactions with amyloid-β and tau pathology, and summarize actionable targets and candidate interventions along a "receptor-intracellular signaling-inflammasome-effector" axis, to inform earlier-stage detection and mechanism-guided intervention in AD.

SARS-CoV-2 infection leads to extrapulmonary complications in multiple organs, including the brain, both in the short-term and long-term. The neurological manifestation of SARS-CoV-2 infection ranges from benign signs like loss of smell and loss of taste to severe complications like encephalitis, stroke, and exacerbation of Alzheimer's disease (AD) progression. Pericytes are mural cells of the brain vasculature that help maintain the blood-brain barrier (BBB), regulate cerebral blood flow (CBF), modulate neuroinflammation, and clear toxic materials, including amyloid beta. Pericytes express ACE2, the receptor for SARS-CoV-2, and therefore may be targeted by either direct virus infection or virus-induced inflammatory cytokines induced by the virus in the brain. To further study the effects of SARS-CoV-2 on pericytes and BBB integrity, the long-term effects of SARS-CoV-2 infection on brain pericytes, inflammation, and other neuropathological complications were analyzed in mice. K18 (human ACE2 transgenic) mice were infected with 10[3] PFU of SARS-CoV-2 (delta strain), and the brains were analyzed at 6, 14, and 30 days post-infection (dpi). A significant reduction in the weight of infected mice was observed by 6 dpi. Viral nucleocapsid protein and infectious SARS-CoV-2 were observed in the brains of all mice by 6 dpi, and in some mice by 14 dpi, but not at 30 dpi. This observation suggests viral neurotropism with subsequent clearance at later timepoints. Despite virus clearance, the levels of inflammatory mediators, including TNF-α and IFN-γ were significantly elevated up to 30 dpi. We also observed a significant reduction in the level of brain pericytes by 14 dpi up to 30 dpi. Importantly, an increase was observed in the level of Friend Leukemia Integration 1 (FLI-1), a transcription factor known to promote pericyte cell death, from 14 dpi up to 30 dpi. The level of amyloid beta 1-42 was elevated in the brain of infected mice at 6 dpi, and this was maintained up to 30 dpi, and there was a decrease in neuronal density from 14 to 30 dpi. Furthermore, we observed an increased expression of Alzheimer's disease (AD)-associated genes like PSEN1, BACE1, and APP. Furthermore, there was increased activation of several neurodegenerative pathways, including "G alpha (z) signaling pathway", "Apelin muscle signaling pathway", and "G beta-gamma (Gβγ) signaling", in the brains of infected mice compared to control mice. Collectively, the observed neuropathology and unique molecular markers of neurodegenerative disease progression provide a novel mechanism by which COVID-19 may promote dementia/AD by contributing to pericyte loss and BBB dysfunction during infection.