Search Results (209)

Forty per cent of major depression patients are resistant to antidepressant medication. Thus, it is necessary to search for alternative treatments. Melatonin (N-acetyl-5-hydroxytryptamine) enhances neurogenesis and neuronal survival in the adult mouse hippocampal dentate gyrus. Additionally, melatonin stimulates the activity of Ca²⁺/Calmodulin-dependent Kinase II (CaMKII), promoting dendrite formation and neurogenic processes in human olfactory neuronal precursors and rat organotypic cultures. Similarly, ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, modulates CaMKII activity. Importantly, co-treatment of low doses of ketamine (10⁻⁷ M) in combination with melatonin (10⁻⁷ M) produces additive effects on neurogenic responses in olfactory neuronal precursors. Importantly, enhanced neurogenic responses are produced by conventional antidepressants like ISSRs. The goal of this study was to investigate whether hippocampal CaMKII participates in the signaling pathway elicited by combining doses of melatonin with ketamine acutely administered to mice, 30 min before being subjected to the forced swimming test. The results showed that melatonin, in conjunction with ketamine, significantly enhances CaMKII activation and changes its subcellular distribution in the dentate gyrus of the hippocampus. Remarkably, melatonin causes nuclear translocation of the active form of CaMKII. Luzindole, a non-selective MT₁ and MT₂ receptor antagonist, abolished these effects, suggesting that CaMKII is downstream of the melatonin receptor pathway that causes the antidepressant-like effects. These findings provide molecular insights into the combined effects of melatonin and ketamine on neuronal plasticity-related signaling pathways and pave the way for combating depression using combination therapy. Full article

Background: There is growing interest in the potential role of manganese (Mn) in the development of Alzheimer’s Disease and related dementias (ADRD). Methods: In this nested pilot study of a ferroalloy worker cohort, we investigated the impact of chronic occupational Mn exposure on cognitive function through β-amyloid (Aβ) deposition and multi-omics profiling. We evaluated six male Mn-exposed workers (median age 63, exposure duration 31 years) and five historical controls (median age: 60 years), all of whom had undergone brain PET scans. Exposed individuals showed significantly higher Aβ deposition in exposed individuals (p < 0.05). The average annual cumulative respirable Mn was 329.23 ± 516.39 µg/m³ (geometric mean 118.59), and plasma Mn levels were significantly elevated in the exposed group (0.704 ± 0.2 ng/mL) compared to controls (0.397 ± 0.18 in controls). Results: LC-MS/MS-based pathway analyses revealed disruptions in olfactory signaling, mitochondrial fatty acid β-oxidation, biogenic amine synthesis, transmembrane transport, and choline metabolism. Simoa analysis showed notable alterations in ADRD-related plasma biomarkers. Protein microarray revealed significant differences (p < 0.05) in antibodies targeting neuronal and autoimmune proteins, including Aβ (25–35), GFAP, serotonin, NOVA1, and Siglec-1/CD169. Conclusion: These findings suggest Mn exposure is associated with neurodegenerative biomarker alterations and disrupted biological pathways relevant to cognitive decline. Full article

Background: Congenital anosmia (CA) is a rare condition characterized by a lifelong inability to perceive odors, which significantly affects daily life and may be linked to broader neurodevelopmental alterations. This study aimed to investigate structural brain differences in patients with CA using MRI, focusing on gray matter (GM) and white matter (WM) changes and their implications for neurodevelopment. Methods: This retrospective study included 28 patients with CA and 28 age- and gender-matched healthy controls. Patients with CA were diagnosed at a single medical center between 1 January 2001 and 30 August 2024. Controls were randomly selected from an imaging database and had no history of olfactory dysfunction. Brain Magnetic Resonance Imaging (MRI)was analyzed using volumetric analysis in SPM12.GM and WM volumes were quantified across 11 anatomical brain regions based on theWFU_PickAtlas toolbox, including frontal, temporal, parietal, occipital, limbic, sub-lobar, cerebellum (anterior/posterior), midbrain, the pons, and the frontal–temporal junction. Left–right hemispheric comparisons were also conducted. Results: Patients with CA exhibited significantly smaller GM volumes compared to healthy controls (560.6 ± 114.7 cc vs. 693.7 ± 96.3 cc, p < 0.001) but larger WM volumes (554.2 ± 75.4 cc vs. 491.1 ± 79.7 cc, p = 0.015). Regionally, GM reductions were observed in the frontal (131.9 ± 33.7 cc vs. 173.7 ± 27.0 cc, p < 0.001), temporal (81.1 ± 18.4 cc vs. 96.5 ± 14.1 cc, p = 0.001), parietal (52.4 ± 15.2 cc vs. 77.2 ± 12.4 cc, p < 0.001), sub-lobar (57.8 ± 9.7 cc vs. 68.2 ± 10.2 cc, p = 0.001), occipital (39.1 ± 13.0 cc vs. 57.8 ± 8.9 cc, p < 0.001), and midbrain (2.0 ± 0.5 cc vs. 2.3 ± 0.4 cc, p = 0.006) regions. Meanwhile, WM increases were notable in the frontal(152.0 ± 19.9 cc vs. 139.2 ± 24.0 cc, p = 0.027), temporal (71.5 ± 11.5 cc vs. 60.8 ± 9.5 cc, p = 0.001), parietal (75.8 ± 12.4 cc vs. 61.9 ± 11.5 cc, p < 0.001), and occipital (58.7 ± 10.3 cc vs. 41.9 ± 7.9 cc, p < 0.001) lobes. A separate analysis of the left and right hemispheres revealed similar patterns of reduced GM and increased WM volumes in patients with CA across both sides. An exception was noted in the right cerebellum-posterior, where patients with CA showed significantly greater WM volume (5.625 ± 1.667 cc vs. 4.666 ± 1.583 cc, p = 0.026). Conclusions: This study demonstrates widespread structural brain differences in individuals with CA, including reduced GM and increased WM volumes across multiple cortical and sub-lobar regions. These findings suggest that congenital olfactory deprivation may impact brain maturation beyond primary olfactory pathways, potentially reflecting altered synaptic pruning and increased myelination during early neurodevelopment. The involvement of the cerebellum further implies potential adaptations beyond motor functions. These structural differences may serve as potential neuroimaging markers for monitoring CA-associated cognitive or emotional comorbidities. Full article

Flavor, as one of the primary factors that attracts consumers, has always been a crucial indicator for evaluating the quality of food. From processing to final consumption, the conditions that affect consumers’ perception of the aroma of aquatic products can be divided into three stages: aroma formation, release, and signal transmission. Currently, there are few reviews on the formation, release, and perception of aroma in aquatic products, which has affected the product development of aquatic products. This review summarizes aroma formation pathways, the effects of processing methods, characteristic volatile compounds, various identification techniques, aroma-release influencing factors, and the aroma perception mechanisms of aquatic products. The Maillard reaction and lipid oxidation are the main pathways for the formation of aromas in aquatic products. The extraction, identification, and quantitative analysis of volatile compounds reveal the odor changes in aquatic products. The composition of aquatic products and oral processing mainly influence the release of odorants. The characteristic odorants perceived from the nasal cavity should be given more attention. Moreover, the relationship between various olfactory receptors (ORs) and the composition of multiple aromatic compounds remains to be understood. It is necessary to clarify the relationship between nasal cavity metabolism and odor perception, reveal the binding and activation mode of ORs and odor molecules, and establish an accurate aroma prediction model. Full article

Background/Objectives: Olfactory neuroblastoma (ONB), also known as esthesioneuroblastoma, is a rare neuroectodermal malignancy of the nasal cavity characterized by aggressive local invasion and variable metastatic potential, with diverse clinical behavior, often presenting at advanced stages. ONB poses challenges for targeted therapeutic strategies, despite advances in surgical and multimodal treatment strategies, because of the rarity of this disease and the limited understanding of its molecular pathophysiology. Methods: A comprehensive review of genomic, multi-omic, and molecular studies was performed to integrate known targeted sites in ONB with the current understanding of its pathophysiology. Results: Recent genetic and molecular studies have identified significant epigenetic and signaling pathway alterations that are critical in pathogenesis and treatment resistance and may serve as potential therapeutic targets. Additionally, novel discovered immunohistochemical and transcriptomic markers, such as IDH2, NEUROD1, and OTX2, offer improved diagnostic specificity and prognostication. Multi-genomic platforms (i.e., multi-omics), involving the combined integration of transcriptomics, epigenetics, and proteomics findings, have led to several recent insights, including the subclassification of neural and basal genomic subtypes, the identification of key driver mutations, and new insights into disease development. This review synthesizes current knowledge on the molecular landscape of ONB, including its tumor origin, immune microenvironment, genetic alterations, and key molecular pathways involved in its pathogenesis. Conclusions: Future research may benefit from integrating these findings into precision medicine approaches, enabling earlier diagnosis and more accurate prognosis. Full article

Lampreys are primitive fish that rely significantly on olfactory cues throughout their complex life cycle. The olfactory system of the sea lamprey (Petromyzon marinus) is among the best characterized in vertebrates. In recent decades, tremendous advances have been made by isolating individual compounds from sea lampreys that can replicate natural behavior when artificially applied in the wild. In no other aquatic vertebrate has the olfactory ecology been described in such extensive detail. In the first section, we provide a comprehensive review of olfactory behaviors induced by specific, individual odorants during every major developmental stage of the sea lamprey in behavioral contexts such as feeding, predator avoidance, and reproduction. Moreover, pheromonal inputs have been shown to induce neuroendocrine responses through the hypothalamic-pituitary-gonadal axis, triggering remarkable developmental and physiological effects, such as gametogenesis and increased pheromone release. In the second section of this review, we describe a hypothetical endocrine signaling pathway through which reproductive fitness is increased following pheromone detection. In the final section of this review, we focus on the neuronal circuits that transform olfactory inputs into motor output. We describe specific brain signaling pathways that underlie odor-evoked locomotion. Furthermore, we consider possible modulatory inputs to these pathways that may induce plasticity in olfactory behavior following changes in the external or internal environment. As a whole, this review synthesizes previous and recent progress in understanding the behavioral, endocrine, and neuronal responses of lampreys to chemosensory signals. Full article

Nose-to-brain drug delivery is an innovative approach that leverages the unique anatomical pathways connecting the nasal cavity to the brain, including the olfactory and trigeminal nerve routes. This method bypasses the blood–brain barrier, enabling direct and efficient transport of therapeutic agents to the central nervous system. It offers significant advantages, such as rapid drug action, reduced systemic side effects, and improved patient compliance through non-invasive administration. This entry summarizes factors affecting the nose-to-brain delivery of drugs and the recent development of nanoparticle-based nose-to-brain delivery. Full article

The Junggar Bactrian camel, a primitive indigenous breed in China, exhibits low reproductive efficiency under natural grazing conditions. This is partly attributed to the development of the epididymis and the quality of semen, both of which directly affect reproductive performance. The epididymis is a key male reproductive organ responsible for sperm storage and transport. However, the gene expression profile of camel epididymal tissue remains poorly understood. In this study, we conducted whole-transcriptome sequencing of epididymal tissues from Junggar Bactrian camels before and after sexual maturity. A total of 683 differentially expressed mRNAs (DEmRNAs) were identified, including TPM2, ITGA5, FASN, and ACP5, of which 415 were upregulated and 268 were downregulated. Additionally, 260 differentially expressed long non-coding RNAs (DELncRNAs), including LOC123611838, LOC105083505, and LOC123614702, were identified, with 113 upregulated and 147 downregulated. An additional 11 differentially expressed microRNAs (DEmiRNAs), including eca-miR-206 and eca-miR-216a, were also detected. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that key differentially expressed genes (DEGs), including TPM2, ITGA5, DDIT4, FASN, and ACP5, were mainly involved in pathways such as Cell Adhesion Molecules, Phospholipase D signaling, Cytokine–Cytokine Receptor Interaction, and Olfactory Transduction. This study presents a comprehensive whole-transcriptome analysis of the epididymis in Junggar Bactrian camels before and after sexual maturity, identifying key genes and regulatory pathways associated with epididymal development and reproductive function. These findings provide a theoretical foundation and valuable data for future research on reproductive performance and epididymal biology in Bactrian camels. Full article

Background: Membranous nephropathy (MN), a prevalent glomerular disorder, remains poorly understood in terms of its association with mitochondrial dynamics (MD). This study investigated the mechanistic involvement of mitochondrial dynamics-related genes (MDGs) in the pathogenesis of MN. Methods: Comprehensive bioinformatics analyses—encompassing Mendelian randomization, machine-learning algorithms, and single-cell RNA sequencing (scRNA-seq)—were employed to interrogate transcriptomic datasets (GSE200828, GSE73953, and GSE241302). Core MDGs were further validated using reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Results: Four key MDGs—RTTN, MYO9A, USP40, and NFKBIZ—emerged as critical determinants, predominantly enriched in olfactory transduction pathways. A nomogram model exhibited exceptional diagnostic performance (area under the curve [AUC] = 1). Seventeen immune cell subsets, including regulatory T cells and activated dendritic cells, demonstrated significant differential infiltration in MN. Regulatory network analyses revealed ATF2 co-regulation mediated by RTTN and MYO9A, along with RTTN-driven modulation of ELOA-AS1 via hsa-mir-431-5p. scRNA-seq analysis identified mesenchymal–epithelial transitioning cells as key contributors, with pseudotime trajectory mapping indicating distinct temporal expression profiles: NFKBIZ (initial upregulation followed by decline), USP40 (gradual fluctuation), and RTTN (persistently low expression). RT-qPCR results corroborated a significant downregulation of all four genes in MN samples compared to controls (p < 0.05). Conclusions: These findings elucidate the molecular underpinnings of MDG-mediated mechanisms in MN, revealing novel diagnostic biomarkers and therapeutic targets. The data underscore the interplay between mitochondrial dynamics and immune dysregulation in MN progression, providing a foundation for precision medicine strategies. Full article

As population aging becomes an increasingly critical global issue, the incidence of central nervous system (CNS) diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke, has risen sharply. However, the blood–brain barrier (BBB) presents a significant obstacle to the effective treatment of these CNS disorders, limiting the ability of therapeutic agents to reach the brain. In this context, intranasal drug delivery, which bypasses the BBB, has attracted considerable attention in recent years. By utilizing pathways such as the olfactory and trigeminal nerves, intranasal drug delivery facilitates the rapid transport of drugs to the brain, thereby enhancing both the bioavailability and targeting efficiency of the drugs. This review provides an overview of the molecular mechanisms underlying intranasal drug delivery, its advancements in the treatment of CNS diseases, strategies to improve delivery efficiency, and a discussion of the challenges and potential future directions in this field. The aim of this paper is to offer valuable insights and guidance for researchers and clinicians working in the area of CNS disease treatment. Full article

Odorant receptors (ORs) constitute the largest family of G protein-coupled receptors (GPCRs), with nearly 400 receptors identified in humans. The “omics” era has revealed an unexpected expression of ORs beyond olfactory tissues. For many decades these receptors were neglected from cancer research, largely due to the assumption that their expression in cancerous tissues was a background leakage, unrelated to conventional cancer pathways such as cell replication, differentiation, or DNA damage response. The Cancer Genome Atlas (TCGA) data shows, however, that OR expression profiles are specific to each tumor type. This evidence supports that ORs may be related to tumor malignancy. In this review, we explore the extranasal expression of ORs in cancer and discuss the potential implications of their presence in cancerous tissues. Full article

Brain ischemia-reperfusion (IR) injury is a critical pathological process that leads to extensive neuronal death, with hippocampal pyramidal cells, particularly those in the cornu Ammonis 1 (CA1) subfield, being highly vulnerable. Until now, human olfactory mitral cell resistance to IR injury has not been directly studied, but olfactory dysfunction in humans is frequently reported in systemic vascular conditions such as ischemic heart failure and may serve as an early clinical marker of neurological or cardiovascular disease. Mitral cells, the principal neurons of the olfactory bulb (OB), exhibit remarkable resistance to IR injury, suggesting the presence of unique molecular adaptations that support their survival under ischemic stress. Several factors may contribute to the resilience of mitral cells. They have a lower susceptibility to excitotoxicity, mitigating the harmful effects of excessive glutamate signaling. Additionally, they maintain efficient calcium homeostasis, preventing calcium overload—a major trigger for cell death in vulnerable neurons. Mitral cells may also express high baseline levels of antioxidant enzymes and their activities, counteracting oxidative stress. Their robust mitochondrial function enhances energy production and reduces susceptibility to metabolic failure. Furthermore, neuroprotective signaling pathways, including phosphatidylinositol-3-kinase (PI3K)/Akt, mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), and nuclear factor erythroid-2-related factor 2 (Nrf2)-mediated antioxidative responses, further bolster their resistance. In addition to these intrinsic mechanisms, the unique microvascular architecture and metabolic support within the olfactory bulb provide an extra layer of protection. By comparing mitral cells to ischemia-sensitive neurons, key vulnerabilities—such as oxidative stress, excitotoxicity, calcium dysregulation, and mitochondrial dysfunction—can be identified and potentially mitigated in other brain regions. Understanding these molecular determinants of neuronal survival may offer valuable insights for developing novel neuroprotective strategies to combat IR injury in highly vulnerable areas, such as the hippocampus and cortex. Full article

Entomopathogenic fungi (EPFs) can influence plant–insect interactions through complex molecular and chemical mechanisms. This study investigates how EPF treatment of tomato plants modulates volatile organic compound (VOC) emissions and subsequent trophic interactions between tomato plants, the herbivorous pest Phthorimaea absoluta, and the parasitic wasp, Trichogramma chilonis. Our results demonstrate that EPF-treated plants exhibited reduced attractiveness to adult P. absoluta moths, which were actively repelled by EPF-induced VOCs. Conversely, these same plants showed enhanced recruitment of the parasitoid T. chilonis, which demonstrated positive chemotaxis toward the modified VOC profile. Chemical analysis revealed significantly elevated emissions of key VOCs in EPF-treated plants, particularly (E)-β-Caryophyllene, β-phellandrene, and α-Phellandrene. This increase is correlated with enhanced production of defense-related phytohormones, including JA, SA, and JA-Ile, which may regulate VOC biosynthesis pathways. Behavioral response studies using synthetic VOCs and electroantennogram (EAG) measurements confirmed that these EPF-induced VOCs elicited strong olfactory responses in both insect species. To summarize, EPF treatment reshapes multitrophic interactions by strategically modulating plant VOC emissions and activating defense signaling pathways in tomato plants, providing new insights for potential applications in sustainable pest management strategies. 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

In recent decades, nose-to-brain drug delivery has shown effectiveness in treating many central nervous system diseases. Intranasally administered drugs can be delivered to the brain through the olfactory and trigeminal pathways that bypass the blood–brain barrier. However, nose-to-brain drug delivery is challenging due to the inadequate nasal mucosa absorption of drugs and the short retention time of the intranasal formulations. These problems can be minimized through the use of nano-drug delivery systems, such as micelles, polymeric nanoparticles, nanoemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers. They can enhance the drug’s bioavailability in the brain via increases in drug solubility, permeation, and stability. Nose-to-brain nano-drug delivery systems have been evaluated in vivo by a number of research groups. This review aims to provide an overview of nose-to-brain delivery and recent advances in the development of nano-drug delivery systems for delivering drugs from the nose to the brain to improve the treatment of some central nervous system diseases. Full article