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Cerebral Cortex (New York, N.Y. : 1991) Nov 2023Olfaction is a crucial sense that is essential for the well-being and survival of individuals. Olfactory bulb (OB) is the first olfactory relay station, and its function... (Review)
Review
Olfaction is a crucial sense that is essential for the well-being and survival of individuals. Olfactory bulb (OB) is the first olfactory relay station, and its function depends on newly generated neurons from the subventricular zone (SVZ). These newly born neurons constantly migrate through the rostral migratory stream to integrate into existing neural networks within the OB, thereby contributing to olfactory information processing. However, the mechanisms underlying the contribution of SVZ adult neurogenesis to OB neurogenesis remain largely elusive. Adult neurogenesis is a finely regulated multistep process involving the proliferation of adult neural stem cells (aNSCs) and neural precursor cells, as well as the migration and differentiation of neuroblasts, and integration of newly generated neurons into preexisting neuronal circuitries. Recently, extensive studies have explored the mechanism of SVZ and OB neurogenesis. This review focused on elucidating various molecules and signaling pathways associated with OB neurogenesis dependent on the SVZ function. A better understanding of the mechanisms underlying the OB neurogenesis on the adult brain is an attractive prospect to induce aNSCs in SVZ to generate new neurons to ameliorate olfactory dysfunction that is involved in various diseases. It will also contribute to developing new strategies for the human aNSCs-based therapies.
Topics: Humans; Neural Stem Cells; Lateral Ventricles; Olfactory Bulb; Neurons; Neurogenesis; Cell Movement
PubMed: 37746807
DOI: 10.1093/cercor/bhad349 -
Reviews in the Neurosciences Apr 2024While breathing is a vital, involuntary physiological function, the mode of respiration, particularly nasal breathing, exerts a profound influence on brain activity... (Review)
Review
While breathing is a vital, involuntary physiological function, the mode of respiration, particularly nasal breathing, exerts a profound influence on brain activity and cognitive processes. This review synthesizes existing research on the interactions between nasal respiration and the entrainment of oscillations across brain regions involved in cognition. The rhythmic activation of olfactory sensory neurons during nasal respiration is linked to oscillations in widespread brain regions, including the prefrontal cortex, entorhinal cortex, hippocampus, amygdala, and parietal cortex, as well as the piriform cortex. The phase-locking of neural oscillations to the respiratory cycle, through nasal breathing, enhances brain inter-regional communication and is associated with cognitive abilities like memory. Understanding the nasal breathing impact on brain networks offers opportunities to explore novel methods for targeting the olfactory pathway as a means to enhance emotional and cognitive functions.
PubMed: 38579456
DOI: 10.1515/revneuro-2023-0152 -
Journal of Neuroendocrinology Jun 2024Olfaction is the most ancient sense and is needed for food-seeking, danger protection, mating and survival. It is often the first sensory modality to perceive changes in... (Review)
Review
Olfaction is the most ancient sense and is needed for food-seeking, danger protection, mating and survival. It is often the first sensory modality to perceive changes in the external environment, before sight, taste or sound. Odour molecules activate olfactory sensory neurons that reside on the olfactory epithelium in the nasal cavity, which transmits this odour-specific information to the olfactory bulb (OB), where it is relayed to higher brain regions involved in olfactory perception and behaviour. Besides odour processing, recent studies suggest that the OB extends its function into the regulation of food intake and energy balance. Furthermore, numerous hormone receptors associated with appetite and metabolism are expressed within the OB, suggesting a neuroendocrine role outside the hypothalamus. Olfactory cues are important to promote food preparatory behaviours and consumption, such as enhancing appetite and salivation. In addition, altered metabolism or energy state (fasting, satiety and overnutrition) can change olfactory processing and perception. Similarly, various animal models and human pathologies indicate a strong link between olfactory impairment and metabolic dysfunction. Therefore, understanding the nature of this reciprocal relationship is critical to understand how olfactory or metabolic disorders arise. This present review elaborates on the connection between olfaction, feeding behaviour and metabolism and will shed light on the neuroendocrine role of the OB as an interface between the external and internal environments. Elucidating the specific mechanisms by which olfactory signals are integrated and translated into metabolic responses holds promise for the development of targeted therapeutic strategies and interventions aimed at modulating appetite and promoting metabolic health.
Topics: Olfactory Bulb; Animals; Humans; Neurosecretory Systems; Feeding Behavior; Smell; Energy Metabolism
PubMed: 38468186
DOI: 10.1111/jne.13382 -
The Journal of Biological Chemistry Nov 2023Microbes living in the intestine can regulate key signaling processes in the central nervous system that directly impact brain health. This gut-brain signaling axis is...
Microbes living in the intestine can regulate key signaling processes in the central nervous system that directly impact brain health. This gut-brain signaling axis is partially mediated by microbe-host-dependent immune regulation, gut-innervating neuronal communication, and endocrine-like small molecule metabolites that originate from bacteria to ultimately cross the blood-brain barrier. Given the mounting evidence of gut-brain crosstalk, a new therapeutic approach of "psychobiotics" has emerged, whereby strategies designed to primarily modify the gut microbiome have been shown to improve mental health or slow neurodegenerative diseases. Diet is one of the most powerful determinants of gut microbiome community structure, and dietary habits are associated with brain health and disease. Recently, the metaorganismal (i.e., diet-microbe-host) trimethylamine N-oxide (TMAO) pathway has been linked to the development of several brain diseases including Alzheimer's, Parkinson's, and ischemic stroke. However, it is poorly understood how metaorganismal TMAO production influences brain function under normal physiological conditions. To address this, here we have reduced TMAO levels by inhibiting gut microbe-driven choline conversion to trimethylamine (TMA), and then performed comprehensive behavioral phenotyping in mice. Unexpectedly, we find that TMAO is particularly enriched in the murine olfactory bulb, and when TMAO production is blunted at the level of bacterial choline TMA lyase (CutC/D), olfactory perception is altered. Taken together, our studies demonstrate a previously underappreciated role for the TMAO pathway in olfactory-related behaviors.
Topics: Animals; Mice; Bacteria; Choline; Methylamines; Olfactory Perception; Female; Mice, Inbred C57BL
PubMed: 37777156
DOI: 10.1016/j.jbc.2023.105299 -
Frontiers in Behavioral Neuroscience 2023Olfaction is a critical sense that allows animals to navigate and understand their environment. In mammals, the critical brain structure to receive and process olfactory... (Review)
Review
Olfaction is a critical sense that allows animals to navigate and understand their environment. In mammals, the critical brain structure to receive and process olfactory information is the olfactory bulb, a structure characterized by a laminated pattern with different types of neurons, some of which project to distant telencephalic structures, like the piriform cortex, the amygdala, and the hippocampal formation. Therefore, the olfactory bulb is the first structure of a complex cognitive network that relates olfaction to different types of memory, including episodic memories. The olfactory bulb continuously adds inhibitory newborn neurons throughout life; these cells locate both in the granule and glomerular layers and integrate into the olfactory circuits, inhibiting projection neurons. However, the roles of these cells modulating olfactory memories are unclear, particularly their role in fear memories. We consider that olfactory neurogenesis might modulate olfactory fear memories by a plastic process occurring in the olfactory bulb.
PubMed: 37840547
DOI: 10.3389/fnbeh.2023.1278324 -
Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants.Nature Communications Jul 2023Anosmia was identified as a hallmark of COVID-19 early in the pandemic, however, with the emergence of variants of concern, the clinical profile induced by SARS-CoV-2...
Anosmia was identified as a hallmark of COVID-19 early in the pandemic, however, with the emergence of variants of concern, the clinical profile induced by SARS-CoV-2 infection has changed, with anosmia being less frequent. Here, we assessed the clinical, olfactory and neuroinflammatory conditions of golden hamsters infected with the original Wuhan SARS-CoV-2 strain, its isogenic ORF7-deletion mutant and three variants: Gamma, Delta, and Omicron/BA.1. We show that infected animals develop a variant-dependent clinical disease including anosmia, and that the ORF7 of SARS-CoV-2 contributes to the induction of olfactory dysfunction. Conversely, all SARS-CoV-2 variants are neuroinvasive, regardless of the clinical presentation they induce. Taken together, this confirms that neuroinvasion and anosmia are independent phenomena upon SARS-CoV-2 infection. Using newly generated nanoluciferase-expressing SARS-CoV-2, we validate the olfactory pathway as a major entry point into the brain in vivo and demonstrate in vitro that SARS-CoV-2 travels retrogradely and anterogradely along axons in microfluidic neuron-epithelial networks.
Topics: Animals; Cricetinae; COVID-19; SARS-CoV-2; Genome, Viral; Axons; Olfactory Bulb; Virus Internalization; Viral Load; Genetic Variation
PubMed: 37495586
DOI: 10.1038/s41467-023-40228-7 -
Current Biology : CB Nov 2023The olfactory bulb (OB) is a critical component of mammalian olfactory neuroanatomy. Beyond being the first and sole relay station for olfactory information to the rest...
The olfactory bulb (OB) is a critical component of mammalian olfactory neuroanatomy. Beyond being the first and sole relay station for olfactory information to the rest of the brain, it also contains elaborate stereotypical circuitry that is considered essential for olfaction. Indeed, substantial lesions of the OB in rodents lead to anosmia. Here, we examined the circuitry that underlies olfaction in a mouse model with severe developmental degeneration of the OB. These mice could perform odor-guided tasks and even responded normally to innate olfactory cues. Despite the near total loss of the OB, piriform cortices in these mice responded to odors, and its neural activity sufficed to decode odor identity. We found that sensory neurons express the full repertoire of olfactory receptors, and their axons project primarily to the rudiments of the OB but also, ectopically, to olfactory cortical regions. Within the OB, the number of principal neurons was greatly reduced, and the morphology of their dendrites was abnormal, extending over large regions within the OB. Glomerular organization was totally lost in the severe cases of OB degeneration and altered in the more conserved OBs. This study shows that olfactory functionality can be preserved despite reduced and aberrant circuitry that is missing many of the elements believed to be essential for olfaction, and it may explain reported retention of olfaction in humans with degenerated OBs.
Topics: Humans; Mice; Animals; Olfactory Bulb; Smell; Olfactory Receptor Neurons; Odorants; Axons; Mammals
PubMed: 37858342
DOI: 10.1016/j.cub.2023.09.061 -
Progress in Neurobiology Sep 2023Olfaction is an important sensory modality for many species and greatly influences animal and human behavior. Still, much about olfactory perception remains unknown. The... (Review)
Review
Olfaction is an important sensory modality for many species and greatly influences animal and human behavior. Still, much about olfactory perception remains unknown. The anterior olfactory nucleus is one of the brain's central early olfactory processing areas. Located directly posterior to the olfactory bulb in the olfactory peduncle with extensive in- and output connections and unique cellular composition, it connects olfactory processing centers of the left and right hemispheres. Almost 20 years have passed since the last comprehensive review on the anterior olfactory nucleus has been published and significant advances regarding its anatomy, function, and pathophysiology have been made in the meantime. Here we briefly summarize previous knowledge on the anterior olfactory nucleus, give detailed insights into the progress that has been made in recent years, and map out its emerging importance in translational research of neurological diseases.
Topics: Animals; Humans; Olfactory Pathways; Olfactory Bulb; Smell; Olfactory Cortex
PubMed: 37343762
DOI: 10.1016/j.pneurobio.2023.102486 -
Ear, Nose, & Throat Journal May 2024The pandemic has affected over 182 million coronavirus disease 2019 (COVID-19) cases worldwide. Accumulated evidence indicates that anosmia is one of the significant... (Review)
Review
OBJECTIVES
The pandemic has affected over 182 million coronavirus disease 2019 (COVID-19) cases worldwide. Accumulated evidence indicates that anosmia is one of the significant characteristics of COVID-19 with a high prevalence. However, many aspects of COVID-19-induced anosmia are still far from being fully understood. The purpose of this review is to summarize recent developments in COVID-19-induced anosmia to increase awareness of the condition.
METHODS
A literature search was carried out using the PubMed, Embase, Web of Science, and Scopus. We reviewed the latest literature on COVID-19-induced anosmia, including mechanisms of pathogenesis, olfactory testing, anosmia as predictive tool, pathological examinations, imaging findings, affected factors, co-existing diseases, treatments, prognosis, hypothesis theories, and future directions.
RESULTS
The possible pathogenesis of COVID-19-induced anosmia may involve inflammation of the olfactory clefts and damage to the olfactory epithelium or olfactory central nervous system by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The D614G spike variant may also play a role in the increased number of anosmia patients. Anosmia may also be an essential indicator of COVID-19 spread and an early indicator of the effectiveness of political decisions. The occurrence and development of COVID-19-induced anosmia may be influenced by smoking behaviors and underlying diseases such as type 2 diabetes, gastroesophageal disorders, and rhinitis. Most patients with COVID-19-induced anosmia can fully or partially recover their olfactory function for varying durations. COVID-19-induced anosmia can be treated with various approaches such as glucocorticoids and olfactory training.
CONCLUSION
Anosmia is one of the main features of COVID-19 and the underlying disease of the patient may also influence its occurrence and development. The possible pathogenesis of COVID-19-induced anosmia is very complicated, which may involve inflammation of the olfactory clefts and damage to the olfactory epithelium or olfactory central nervous system.
Topics: COVID-19; Humans; Anosmia; SARS-CoV-2; Olfactory Mucosa; Olfaction Disorders
PubMed: 34587819
DOI: 10.1177/01455613211048998 -
Amelioration of Cognitive and Olfactory System Deficits in APOE4 Transgenic Mice with DHA Treatment.Molecular Neurobiology Oct 2023Olfactory dysfunction and atrophy of olfactory brain regions are observed early in mild cognitive impairment and Alzheimer disease. Despite substantial evidence showing...
Olfactory dysfunction and atrophy of olfactory brain regions are observed early in mild cognitive impairment and Alzheimer disease. Despite substantial evidence showing neuroprotective effects in MCI/AD with treatment of docosahexaenoic acid (DHA), an omega-3 fatty acid, few studies have assessed DHA and its effects on the olfactory system deficits. We therefore performed structural (MRI), functional (olfactory behavior, novel object recognition), and molecular (markers of apoptosis and inflammation) assessments of APOE4 and wild-type mice ± DHA treatment at 3, 6, and 12 months of age. Our results demonstrate that APOE4 mice treated with the control diet show recognition memory deficits, abnormal olfactory habituation, and discrimination abilities and an increase in IBA-1 immunoreactivity in the olfactory bulb. These phenotypes were not present in APOE4 mice treated with a DHA diet. Alterations in some brain regions' weights and/or volumes were observed in the APOPE4 mice and may be due to caspase activation and/or neuroinflammatory events. These results suggest that the consumption of a diet rich in DHA may provide some benefit to E4 carriers but may not alleviate all symptoms.
Topics: Mice; Animals; Mice, Transgenic; Docosahexaenoic Acids; Apolipoprotein E4; Brain; Cognitive Dysfunction; Alzheimer Disease; Cognition
PubMed: 37329383
DOI: 10.1007/s12035-023-03401-z