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Chemical Senses Jul 2019Cross-modal sensory communication is an innate biological process that refers to the combination and/or interpretation of different types of sensory input in the brain.... (Review)
Review
Cross-modal sensory communication is an innate biological process that refers to the combination and/or interpretation of different types of sensory input in the brain. Often, this process conjugates with neural modulation, by which the neural signals that convey sensory information are adjusted, such as intensity, frequency, complexity, and/or novelty. Although the anatomic pathways involved in cross-modal sensory integration have been previously described, the course of development and the physiological roles of multisensory signaling integration in brain functions remain to be elucidated. In this article, I review some of the recent findings in sensory integration from research using the zebrafish models. In zebrafish, cross-modal sensory integration occurs between the olfactory and visual systems. It is mediated by the olfacto-retinal centrifugal (ORC) pathway, which originates from the terminalis nerve (TN) in the olfactory bulb and terminates in the neural retina. In the retina, the TNs synapse with the inner nuclear layer dopaminergic interplexiform cells (DA-IPCs). Through the ORC pathway, stimulation of the olfactory neurons alters the cellular activity of TNs and DA-IPCs, which in turn modulates retinal neural function and increases behavioral visual sensitivity.
Topics: Animals; Neurons; Olfactory Bulb; Retina; Smell; Zebrafish
PubMed: 31066902
DOI: 10.1093/chemse/bjz022 -
Stem Cell Reports Dec 2023Although adult subependymal zone (SEZ) neural stem cells mostly generate GABAergic interneurons, a small progenitor population expresses the proneural gene Neurog2 and...
Although adult subependymal zone (SEZ) neural stem cells mostly generate GABAergic interneurons, a small progenitor population expresses the proneural gene Neurog2 and produces glutamatergic neurons. Here, we determined whether Neurog2 could respecify SEZ neural stem cells and their progeny toward a glutamatergic fate. Retrovirus-mediated expression of Neurog2 induced the glutamatergic lineage markers TBR2 and TBR1 in cultured SEZ progenitors, which differentiated into functional glutamatergic neurons. Likewise, Neurog2-transduced SEZ progenitors acquired glutamatergic neuron hallmarks in vivo. Intriguingly, they failed to migrate toward the olfactory bulb and instead differentiated within the SEZ or the adjacent striatum, where they received connections from local neurons, as indicated by rabies virus-mediated monosynaptic tracing. In contrast, lentivirus-mediated expression of Neurog2 failed to reprogram early SEZ neurons, which maintained GABAergic identity and migrated to the olfactory bulb. Our data show that NEUROG2 can program SEZ progenitors toward a glutamatergic identity but fails to reprogram their neuronal progeny.
Topics: Basic Helix-Loop-Helix Transcription Factors; Neurons; Neural Stem Cells; Cell Differentiation; Olfactory Bulb; Neurogenesis
PubMed: 37995703
DOI: 10.1016/j.stemcr.2023.10.019 -
Brain Pathology (Zurich, Switzerland) Mar 2022Alzheimer's disease (AD) is the most prevalent form of dementia. Key AD symptoms include memory and cognitive decline; however, comorbid symptoms such as depression and...
Alzheimer's disease (AD) is the most prevalent form of dementia. Key AD symptoms include memory and cognitive decline; however, comorbid symptoms such as depression and sensory-perceptual dysfunction are often reported. Among these, a deterioration of olfactory sensation is observed in approximately 90% of AD patients. However, the precise pathophysiological basis underlying olfactory deficits because of AD remains elusive. The olfactory glomeruli in the olfactory bulb (OB) receive sensory information in the olfactory processing pathway. Maintaining the structural and functional integrity of the olfactory glomerulus is critical to olfactory signalling. Herein, we conducted an in-depth histopathological assessment to reveal detailed structural alterations in the olfactory glomeruli in AD patients. Fresh frozen post-mortem OB specimens obtained from six AD patients and seven healthy age-matched individuals were examined. We used combined immunohistochemistry and stereology to assess the gross morphology and histological alterations, such as those in the expression of Aβ protein, microglia, and neurotransmitters in the OB. Electron microscopy was employed to study the ultrastructural features in the glomeruli. Significant accumulation of Aβ, morphologic damage, altered neurotransmitter levels, and microgliosis in the olfactory glomeruli of AD patients suggests that glomerular damage could affect olfactory function. Moreover, greater neurodegeneration was observed in the ventral olfactory glomeruli of AD patients. The synaptic ultrastructure revealed distorted postsynaptic densities and a decline in presynaptic vesicles in AD specimens. These findings show that the primary olfactory pathway is affected by the pathogenesis of AD, and may provide clues to identifying the mechanism involved in olfactory dysfunction in AD.
Topics: Alzheimer Disease; Autopsy; Humans; Olfactory Bulb; Smell
PubMed: 34704631
DOI: 10.1111/bpa.13033 -
Folia Morphologica 2022This study aimed to reveal the change in olfactory bulbus volume (OBV) and olfactory sulcus depth (OSD) in healthy Turkish paediatric individuals between 1 month and 18...
BACKGROUND
This study aimed to reveal the change in olfactory bulbus volume (OBV) and olfactory sulcus depth (OSD) in healthy Turkish paediatric individuals between 1 month and 18 years of age with 3 Tesla magnetic resonance imaging (MRI), taking into account different age groups and gender factors.
MATERIALS AND METHODS
In this retrospective study, 190 paediatric individuals who underwent cranial MRI were evaluated. Healthy paediatric cases were divided into four groups as infantile period (first 24 months when cerebral myelinisation was completed), early childhood (2-6 years), childhood (6-12 years) and adolescence (12-18 years). OBV and OSD measurements were performed on coronal T2-weighted brain MRI by 3 Tesla magnetic resonance scan. The mean, right and left OBVs and OSDs were used for evaluation.
RESULTS
The mean age was 9.9 ± 7.5 months for the infantile period, 4.5 ± 1.3 years for early childhood, 9.3 ± 1.7 years for childhood and 15.2 ± 1.7 years for adolescence. Mean, right and left OBV was found to be slightly larger in male children than in female children (p = 0.015, p = 0.033 and p = 0.010, respectively). There was no statistical difference between the genders for mean, right and left OSD (p = 0.559, p = 0.536 and p = 0.598, respectively). Among the age groups, the values of the 3rd and 4th groups in terms of mean, right and left OBV were higher than in the other two groups (p < 0.001). In terms of OSD, mean, right and left values were higher in group 2, 3 and 4 than in group 1 (p < 0.001).
CONCLUSIONS
These data differ by paediatric age group and gender for the development of OBV and OSD. Normal values for the paediatric age group and gender should be calculated to detect olfactory dysfunction.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Olfaction Disorders; Olfactory Bulb; Prefrontal Cortex; Retrospective Studies
PubMed: 33749801
DOI: 10.5603/FM.a2021.0022 -
Cell and Tissue Research Jan 2021Evolutionarily, olfaction is one of the oldest senses and pivotal for an individual's health and survival. The olfactory bulb (OB), as the first olfactory relay station... (Review)
Review
Evolutionarily, olfaction is one of the oldest senses and pivotal for an individual's health and survival. The olfactory bulb (OB), as the first olfactory relay station in the brain, is known to heavily process sensory information. To adapt to an animal's needs, OB activity can be influenced by many factors either from within (intrinsic neuromodulation) or outside (extrinsic neuromodulation) the OB which include neurotransmitters, neuromodulators, hormones, and neuropeptides. Extrinsic sources seem to be of special importance as the OB receives massive efferent input from numerous brain centers even outweighing the sensory input from the nose. Here, we review neuromodulatory processes in the rodent OB from such extrinsic sources. We will discuss extrinsic neuromodulation according to points of origin, receptors involved, affected circuits, and changes in behavior. In the end, we give a brief outlook on potential future directions in research on neuromodulation in the OB.
Topics: Animals; Olfactory Bulb; Rodentia
PubMed: 33355709
DOI: 10.1007/s00441-020-03365-9 -
International Journal of Molecular... Apr 2020Endocannabinoid synthesis in the human body is naturally occurring and on-demand. It occurs in response to physiological and environmental stimuli, such as stress,... (Review)
Review
Endocannabinoid synthesis in the human body is naturally occurring and on-demand. It occurs in response to physiological and environmental stimuli, such as stress, anxiety, hunger, other factors negatively disrupting homeostasis, as well as the therapeutic use of the phytocannabinoid cannabidiol and recreational use of exogenous cannabis, which can lead to cannabis use disorder. Together with their specific receptors CB1R and CB2R, endocannabinoids are major components of endocannabinoid-mediated neuromodulation in a rapid and sustained manner. Extensive research on endocannabinoid function and expression includes studies in limbic system structures such as the hippocampus and amygdala. The wide distribution of endocannabinoids, their on-demand synthesis at widely different sites, their co-existence in specific regions of the body, their quantitative differences in tissue type, and different pathological conditions indicate their diverse biological functions that utilize specific and overlapping pathways in multiple organ systems. Here, we review emerging evidence of these pathways with a special emphasis on the role of endocannabinoids in decelerating neurodegenerative pathology through neural networks initiated by cells in the main olfactory bulb.
Topics: Animals; Disease Susceptibility; Endocannabinoids; Humans; Neurodegenerative Diseases; Neuronal Plasticity; Neurons; Olfactory Bulb; Signal Transduction
PubMed: 32325875
DOI: 10.3390/ijms21082850 -
Anatomical Record (Hoboken, N.J. : 2007) Feb 2023Cell migration from the olfactory placode (OP) is a well-known phenomenon wherein various cell types, such as gonadotropin-releasing hormone (GnRH)-producing neurons,...
Cell migration from the olfactory placode (OP) is a well-known phenomenon wherein various cell types, such as gonadotropin-releasing hormone (GnRH)-producing neurons, migrate toward the telencephalon (TEL) during early embryonic development. However, the spatial relationship between early migratory cells and the forebrain is unclear. We examined the early development of whole-mount chick embryos to observe the three-dimensional spatial relationship among OP-derived migratory neurons, olfactory nerve (ON), and TEL. Migratory neurons that express highly polysialylated neural cell adhesion molecule (PSA-NCAM) emerge from the OP and spread over a relatively wide TEL area at the Hamburger and Hamilton (HH) stage 17. Most migratory neurons form a cellular cord between the olfactory pit and rostral TEL within HH18-20. The earliest axons from the olfactory epithelium (OE) were detected along this neuronal cord using DiI-labeling at HH21. Furthermore, a few PSA-NCAM-positive neurons were dispersed around the cellular cord and over the lateral TEL at HH18. A long cellular cord branch extending to the lateral TEL was transiently observed within HH18-24. These results suggest a novel migratory route of OP-derived neurons during the early developmental stages. Following GFP vector introduction into the OP of HH13-15 embryos, labeled neurons were detected around and within the lateral TEL at HH23 and HH27. At HH36, labeled cells were observed in the rostral-lateral TEL, including the olfactory bulb (OB) region. GFP-labeled and calretinin-positive neurons were detected in the OB, suggesting that early OP-derived neurons enter the forebrain and function as interneurons in the OB.
Topics: Animals; Chick Embryo; Axons; Cell Movement; Neurons; Olfactory Bulb; Olfactory Nerve; Prosencephalon; Telencephalon
PubMed: 36104941
DOI: 10.1002/ar.25080 -
The European Journal of Neuroscience Feb 2022The olfactory system has become an important functional gateway to understand and analyze neuromodulation since olfactory dysfunction and deficits have emerged as... (Review)
Review
The olfactory system has become an important functional gateway to understand and analyze neuromodulation since olfactory dysfunction and deficits have emerged as prodromal and, at other times, as first symptoms of many of neurodegenerative, neuropsychiatric and communication disorders. Considering olfactory dysfunction as outcome of altered, damaged and/or inefficient olfactory processing, in the current review, we analyze how olfactory processing interacts with the endocannabinoid signaling system. In the human body, endocannabinoid synthesis is a natural and on-demand response to a wide range of physiological and environmental stimuli. Our current understanding of the response dynamics of the endocannabinoid system is based in large part on research advances in limbic system areas, such as the hippocampus and the amygdala. Functional interactions of this signaling system with olfactory processing and associated pathways are just emerging but appear to grow rapidly with multidimensional approaches. Recent work analyzing the crystal structure of endocannabinoid receptors bound to their agonists in a signaling complex has opened avenues for developing specific therapeutic drugs that could help with neuroinflammation, neurodegeneration, and alleviation/reduction of pain. We discuss the role of endocannabinoids as signaling molecules in the olfactory system and the relevance of the endocannabinoid system for synaptic plasticity.
Topics: Endocannabinoids; Humans; Neuronal Plasticity; Olfaction Disorders; Olfactory Bulb; Smell
PubMed: 33724578
DOI: 10.1111/ejn.15186 -
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 -
International Journal of Molecular... Jul 2021Parkinson's disease (PD) is the most common movement disorder, characterized by progressive degeneration of the nigrostriatal pathway, which consists of dopaminergic...
Parkinson's disease (PD) is the most common movement disorder, characterized by progressive degeneration of the nigrostriatal pathway, which consists of dopaminergic cell bodies in substantia nigra and their neuronal projections to the striatum. Moreover, PD is associated with an array of non-motor symptoms such as olfactory dysfunction, gastrointestinal dysfunction, impaired regulation of the sleep-wake cycle, anxiety, depression, and cognitive impairment. Inflammation and concomitant oxidative stress are crucial in the pathogenesis of PD. Thus, this study aimed to model PD via intrastriatal injection of the inflammagen lipopolysaccharide (LPS)to investigate if the lesion causes olfactory and motor impairments, inflammation, oxidative stress, and alteration in synaptic proteins in the olfactory bulb, striatum, and colon. Ten µg of LPS was injected unilaterally into the striatum of 27 male C57BL/6 mice, and behavioural assessment was conducted at 4 and 8 weeks post-treatment, followed by tissue collection. Intrastriatal LPS induced motor impairment in C57BL/6 mice at 8 weeks post-treatment evidenced by reduced latency time in the rotarod test. LPS also induced inflammation in the striatum characterized by increased expression of microglial marker Iba-1 and astrocytic marker GFAP, with degeneration of dopaminergic neuronal fibres (reduced tyrosine hydroxylase immunoreactivity), and reduction of synaptic proteins and DJ-1 protein. Additionally, intrastriatal LPS induced inflammation, oxidative stress and alterations in synaptic proteins within the olfactory bulb, although this did not induce a significant impairment in olfactory function. Intrastriatal LPS induced mild inflammatory changes in the distal colon, accompanied by increased protein expression of 3-nitrotyrosine-modified proteins. This model recapitulated the major features of PD such as motor impairment and degeneration of dopaminergic neuronal fibres in the striatum, as well as some pathological changes in the olfactory bulb and colon; thus, this model could be suitable for understanding clinical PD and testing neuroprotective strategies.
Topics: Animals; Astrocytes; Behavior Rating Scale; Brain-Derived Neurotrophic Factor; Calcium-Binding Proteins; Colon; Corpus Striatum; Disease Models, Animal; Dopaminergic Neurons; Glial Fibrillary Acidic Protein; Immunohistochemistry; Inflammation; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Microfilament Proteins; Microglia; Olfactory Bulb; Oxidative Stress; Parkinson Disease; Protein Deglycase DJ-1; Reactive Oxygen Species; Substantia Nigra; Tyrosine 3-Monooxygenase; alpha-Synuclein
PubMed: 34299000
DOI: 10.3390/ijms22147380