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International Journal of Molecular... Apr 2021Severe acute respiratory syndrome (SARS) coronavirus‑2 (SARS‑CoV‑2), the causative viral agent for the ongoing COVID‑19 pandemic, enters its host cells primarily...
Severe acute respiratory syndrome (SARS) coronavirus‑2 (SARS‑CoV‑2), the causative viral agent for the ongoing COVID‑19 pandemic, enters its host cells primarily via the binding of the SARS‑CoV‑2 spike (S) proteins to the angiotensin‑converting enzyme 2 (ACE2). A number of other cell entry mediators have also been identified, including neuropilin‑1 (NRP1) and transmembrane protease serine 2 (TMPRSS2). More recently, it has been demonstrated that transmembrane protease serine 4 (TMPRSS4) along with TMPRSS2 activate the SARS‑CoV‑2 S proteins, and enhance the viral infection of human small intestinal enterocytes. To date, a systematic analysis of TMPRSS4 in health and disease is lacking. In the present study, using tools, the gene expression and genetic alteration of TMPRSS4 were analysed across numerous tumours and compared to controls. The observations were also expanded to the level of the central nervous system (CNS). The findings revealed that TMPRSS4 was overexpressed in 11 types of cancer, including lung adenocarcinoma, lung squamous cell carcinoma, cervical squamous cell carcinoma, thyroid carcinoma, ovarian cancer, cancer of the rectum, pancreatic cancer, colon and stomach adenocarcinoma, uterine carcinosarcoma and uterine corpus endometrial carcinoma, whilst it was significantly downregulated in kidney carcinomas, acute myeloid leukaemia, skin cutaneous melanoma and testicular germ cell tumours. Finally, a high TMPRSS4 expression was documented in the olfactory tubercle, paraolfactory gyrus and frontal operculum, all brain regions which are associated with the sense of smell and taste. Collectively, these data suggest that TMPRSS4 may play a role in COVID‑19 symptomatology as another SARS‑CoV‑2 host cell entry mediator responsible for the tropism of this coronavirus both in the periphery and the CNS.
Topics: Brain; COVID-19; Central Nervous System; Computer Simulation; Databases, Genetic; Female; Gastrointestinal Tract; Gene Expression Profiling; Host Microbial Interactions; Humans; Male; Membrane Proteins; Neoplasms; Pandemics; SARS-CoV-2; Serine Endopeptidases; Virus Internalization
PubMed: 33649798
DOI: 10.3892/ijmm.2021.4897 -
Progress in Neurobiology Jun 2021During mammalian evolution, primate neocortex expanded, shifting hippocampal functional networks away from primary sensory cortices, towards association cortices....
During mammalian evolution, primate neocortex expanded, shifting hippocampal functional networks away from primary sensory cortices, towards association cortices. Reflecting this rerouting, human resting hippocampal functional networks preferentially include higher association cortices, while those in rodents retained primary sensory cortices. Research on human visual, auditory and somatosensory systems shows evidence of this rerouting. Olfaction, however, is unique among sensory systems in its relative structural conservation throughout mammalian evolution, and it is unknown whether human primary olfactory cortex was subject to the same rerouting. We combined functional neuroimaging and intracranial electrophysiology to directly compare hippocampal functional networks across human sensory systems. We show that human primary olfactory cortex-including the anterior olfactory nucleus, olfactory tubercle and piriform cortex-has stronger functional connectivity with hippocampal networks at rest, compared to other sensory systems. This suggests that unlike other sensory systems, olfactory-hippocampal connectivity may have been retained in mammalian evolution. We further show that olfactory-hippocampal connectivity oscillates with nasal breathing. Our findings suggest olfaction might provide insight into how memory and cognition depend on hippocampal interactions.
Topics: Brain Mapping; Cerebral Cortex; Hippocampus; Humans; Olfactory Cortex; Sense Organs; Smell
PubMed: 33640412
DOI: 10.1016/j.pneurobio.2021.102027 -
Current Biology : CB Apr 2021Pleasant odorants are represented in the posterior olfactory bulb (pOB) in mice. How does this hedonic information generate odor-motivated behaviors? Using optogenetics,...
Pleasant odorants are represented in the posterior olfactory bulb (pOB) in mice. How does this hedonic information generate odor-motivated behaviors? Using optogenetics, we report here that stimulating the representation of pleasant odorants in a sensory structure, the pOB, can be rewarding, self-motivating, and is accompanied by ventral tegmental area activation. To explore the underlying neural circuitry downstream of the olfactory bulb (OB), we use 3D high-resolution imaging and optogenetics and determine that the pOB preferentially projects to the olfactory tubercle, whose increased activity is related to odorant attraction. We further show that attractive odorants act as reinforcers in dopamine-dependent place preference learning. Finally, we extend those findings to humans, who exhibit place preference learning and an increase BOLD signal in the olfactory tubercle in response to attractive odorants. Thus, strong and persistent attraction induced by some odorants is due to a direct gateway from the pOB to the reward system.
Topics: Animals; Emotions; Male; Mice; Mice, Inbred C57BL; Motivation; Odorants; Olfactory Bulb; Olfactory Perception; Optogenetics; Reward; Smell
PubMed: 33607032
DOI: 10.1016/j.cub.2021.01.066 -
Frontiers in Neural Circuits 2020Olfaction plays an important role in the evaluation, motivation, and palatability of food. The chemical identity of odorants is coded by a spatial combination of... (Review)
Review
Olfaction plays an important role in the evaluation, motivation, and palatability of food. The chemical identity of odorants is coded by a spatial combination of activated glomeruli in the olfactory bulb, which is referred to as the odor map. However, the functional roles of the olfactory cortex, a collective region that receives axonal projections from the olfactory bulb, and higher olfactory centers in odor-guided eating behaviors are yet to be elucidated. The olfactory tubercle (OT) is a component of the ventral striatum and forms a node within the mesolimbic dopaminergic pathway. Recent studies have revealed the anatomical domain structures of the OT and their functions in distinct odor-guided motivated behaviors. Another component of the ventral striatum, the nucleus accumbens, is well known for its involvement in motivation and hedonic responses for foods, which raises the possibility of functional similarities between the OT and nucleus accumbens in eating. This review first summarizes recent findings on the domain- and neuronal subtype-specific roles of the OT in odor-guided motivated behaviors and then proposes a model for the regulation of eating behaviors by the OT.
Topics: Animals; Feeding Behavior; Humans; Motivation; Nucleus Accumbens; Odorants; Olfactory Tubercle
PubMed: 33262693
DOI: 10.3389/fncir.2020.577880 -
Clinical Neuroradiology Mar 2021The anterior perforating arteries are a group of arteries that enter the brain through the anterior perforated substance (APS). Because the lenticulostriate artery, the... (Review)
Review
Embryological Lateral Striate Artery Variants : Revised Concept of Recurrent Artery of Heubner, the Perforators to the Anterior Perforated Substance and Middle Cerebral Artery Variants.
PURPOSE
The anterior perforating arteries are a group of arteries that enter the brain through the anterior perforated substance (APS). Because the lenticulostriate artery, the recurrent artery of Heubner (RAH) and the perforators from A1 of anterior cerebral artery (ACA) penetrate the APS and supply the basal ganglia, these arteries can be considered as having a common embryological origin.
RESULTS
During development, the lateral striate arteries are divided from the lateral olfactory artery and divided into the RAH and middle cerebral artery (MCA). The RAH is a fascinating artery for its early development and variations of origin and course. The MCA has also several variations, such as the duplicated MCA, accessory MCA, and fenestration.
CONCLUSION
We provide a review of embryologic development and anatomical variations of the RAH, the perforators to the APS and MCA as a group of the lateral striate artery.
Topics: Anterior Cerebral Artery; Basal Ganglia; Brain; Cerebral Arteries; Humans; Middle Cerebral Artery; Olfactory Tubercle
PubMed: 33245401
DOI: 10.1007/s00062-020-00978-z -
Journal of Neurophysiology Jan 2021The ventral striatum regulates motivated behaviors that are essential for survival. The ventral striatum contains both the nucleus accumbens (NAc), which is well...
The ventral striatum regulates motivated behaviors that are essential for survival. The ventral striatum contains both the nucleus accumbens (NAc), which is well established to contribute to motivated behavior, and the adjacent tubular striatum (TuS), which is poorly understood in this context. We reasoned that these ventral striatal subregions may be uniquely specialized in their neural representation of goal-directed behavior. To test this, we simultaneously examined TuS and NAc single-unit activity as male mice engaged in a sucrose self-administration task, which included extinction and cue-induced reinstatement sessions. Although background levels of activity were comparable between regions, more TuS neurons were recruited upon reward-taking, and among recruited neurons, TuS neurons displayed greater changes in their firing during reward-taking and extinction than those in the NAc. Conversely, NAc neurons displayed greater changes in their firing during cue-reinstated reward-seeking. Interestingly, at least in the context of this behavioral paradigm, TuS neural activity predicted reward-seeking, whereas NAc activity did not. Together, by directly comparing their dynamics in several behavioral contexts, this work reveals that the NAc and TuS ventral striatum subregions distinctly represent reward-taking and reward-seeking. The ventral striatum, considered the reward circuitry "hub," is composed of two regions: the NAc, which is well established for its role in reward processing, and the TuS, which has been largely excluded from such studies. This study provides a first step in directly contextualizing the TuS's activity in relation to that in the NAc and, by doing so, establishes a critical framework for future research seeking to better understand the brain basis for drug addiction.
Topics: Animals; Cues; Drug-Seeking Behavior; Goals; Male; Mice; Mice, Inbred C57BL; Neurons; Nucleus Accumbens; Reward
PubMed: 33174477
DOI: 10.1152/jn.00495.2020 -
The Journal of Neuroscience : the... Sep 2020In the mid-19th century, a misconception was born, which understandably persists in the minds of many neuroscientists today. The eminent scientist Albert von Kölliker... (Review)
Review
In the mid-19th century, a misconception was born, which understandably persists in the minds of many neuroscientists today. The eminent scientist Albert von Kölliker named a tubular-shaped piece of tissue found in the brains of all mammals studied to date, the tuberculum olfactorium - or what is commonly known as the olfactory tubercle (OT). In doing this, Kölliker ascribed "olfactory" functions and an "olfactory" purpose to the OT. The OT has since been classified as one of several olfactory cortices. However, further investigations of OT functions, especially over the last decade, have provided evidence for roles of the OT beyond olfaction, including in learning, motivated behaviors, and even seeking of psychoactive drugs. Indeed, research to date suggests caution in assigning the OT with a purely olfactory role. Here, I build on previous research to synthesize a model wherein the OT, which may be more appropriately termed the "tubular striatum" (TuS), is a neural system in which sensory information derived from an organism's experiences is integrated with information about its motivational states to guide affective and behavioral responses.
Topics: Animals; Corpus Striatum; Humans; Olfactory Perception
PubMed: 32968026
DOI: 10.1523/JNEUROSCI.1109-20.2020 -
IBRO Reports Dec 2020The tenia tecta is extensively interconnected with the main olfactory bulb and olfactory cortical areas and is well positioned to contribute to olfactory processing....
The tenia tecta is extensively interconnected with the main olfactory bulb and olfactory cortical areas and is well positioned to contribute to olfactory processing. However, little is known about odor representation within its dorsal (DTT) and ventral (VTT) components. To address this need, spontaneous and odor-evoked activity of DTT and VTT neurons was recorded from urethane anesthetized mice and compared to activity recorded from adjacent areas within adjacent caudomedial aspects of the anterior olfactory nucleus (AON). Neurons recorded from DTT, VTT, and AON exhibited odor-selective alterations in firing rate in response to a diverse set of monomolecular odorants. While DTT and AON neurons exhibited similar tuning breadth, selectivity, and response topography, the proportion of odor-selective neurons was substantially higher in the DTT. These findings provide evidence that the tenia tecta may contribute to the encoding of specific stimulus attributes. Further work is needed to fully characterize functional organization of the tenia tecta and its contribution to sensory representation and utilization.
PubMed: 32793841
DOI: 10.1016/j.ibror.2020.07.010 -
Cell Reports Jul 2020Odors are well known to elicit strong emotional and behavioral responses that become strengthened throughout learning, yet the specific cellular systems involved in odor...
Odors are well known to elicit strong emotional and behavioral responses that become strengthened throughout learning, yet the specific cellular systems involved in odor learning and the direct influence of these on behavior are unclear. Here, we investigate the representation of odor-reward associations within two areas recipient of dense olfactory input, the posterior piriform cortex (pPCX) and the olfactory tubercle (OT), using electrophysiological recordings from mice engaged in reward-based learning. Neurons in both regions represent conditioned odors and do so with similar information content, yet the proportion of neurons recruited by conditioned rewarded odors and the magnitudes and durations of their responses are greater in the OT. Using fiber photometry, we find that OT D1-type dopamine-receptor-expressing neurons flexibly represent odors based on reward associations, and using optogenetics, we show that these neurons influence behavioral engagement. These findings contribute to a model whereby OT D1 neurons support odor-guided motivated behaviors.
Topics: Animals; Behavior, Animal; Male; Mice, Inbred C57BL; Neural Pathways; Neurons; Olfactory Tubercle; Piriform Cortex; Receptors, Dopamine D1; Reward; Smell
PubMed: 32697986
DOI: 10.1016/j.celrep.2020.107919 -
Journal of Neuroimmune Pharmacology :... Jun 2021MP-10 (PF-2545920) is a selective inhibitor of phosphodiesterase 10A (PDE10A), an enzyme highly enriched in the striatum, nucleus accumbens, olfactory tubercle, and...
MP-10 (PF-2545920) is a selective inhibitor of phosphodiesterase 10A (PDE10A), an enzyme highly enriched in the striatum, nucleus accumbens, olfactory tubercle, and substantia nigra. The therapeutic effect of MP-10 has been reported in psychiatric and neurodegenerative disorders such as schizophrenia, depression, and Huntington's disease. However, the effect of MP-10 in Parkinson's disease (PD) has not been reported to date. In this study, we examined the effect of MP-10 in neuroinflammation and PD mouse models. MP-10 inhibited nitric oxide, tumor necrosis factor alpha, and interleukin (IL)-6 production, while it promoted IL-10 production in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Subsequent western blot and reverse transcription polymerase chain reaction analyses showed that MP-10 reduced the mRNA and protein levels of inducible nitric oxide synthase, cyclooxygenase-2, proinflammatory cytokines, and matrix metalloproteinase-3, -8, and - 9 in LPS-stimulated BV2 cells. Further mechanistic studies revealed that MP-10 exerts anti-inflammatory effects by inhibiting the phosphorylation of c-Jun N-terminal kinase and Akt, reducing the activity of nuclear factor-kappa B/activator protein-1, and upregulating the nuclear factor erythroid 2-related factor 2/antioxidant response element and protein kinase A/cAMP response element-binding protein signaling pathways. The anti-inflammatory effect of MP-10 was confirmed in vivo. Specifically, MP-10 inhibited microglial activation and proinflammatory gene expression in the brains of LPS-injected mice. Moreover, MP-10 rescued behavioral deficits and recovered dopaminergic neuronal cell death in the brains of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice. MP-10 also reduced microglial activation in this PD mouse model. These data collectively suggest that MP-10 may have therapeutic potential in PD and other neuroinflammatory disorders. Graphical Abstract.
Topics: Animals; Anti-Inflammatory Agents; Brain; Inflammation; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Microglia; Parkinsonian Disorders; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Pyrazoles; Quinolines
PubMed: 32671618
DOI: 10.1007/s11481-020-09943-6