Unraveling the Role of CHRNA6, the Neuronal α6 Nicotinic Acetylcholine Receptor Subunit

Receptors, Journal Year: 2025, Volume and Issue: 4(1), P. 1 - 1

Published: Jan. 14, 2025

The increased prevalence of electronic cigarettes, particularly among adolescents, has escalated concerns about nicotine addiction. Nicotine, a potent psychostimulant found in tobacco products, exerts its effects by interacting with nicotinic acetylcholine receptors (nAChRs) the brain. Recent findings both pre-clinical and clinical studies have enhanced our understanding nAChRs, overcoming limitations pharmacological tools that previously hindered their investigation. Of particular interest is α6 subunit, whose expression peaks during adolescence, critical period brain development often marked initiation substance use. Pre-clinical linked α6-containing nAChRs (α6*nAChRs) to nicotine-induced locomotion, dopamine release, self-administration behavior. Furthermore, suggest an association between subunit smoking behavior humans. Specifically, single nucleotide polymorphism 3′ untranslated region CHRNA6 gene encodes for this other A comprehensive subunit’s role addiction high importance. This review aims consolidate current knowledge regarding functions implications disorders, hope paving way future research targeted therapies address pressing public health concern.

Language: Английский

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Heavy Metal Interactions with Neuroglia and Gut Microbiota: Implications for Huntington’s Disease

Cells, Journal Year: 2024, Volume and Issue: 13(13), P. 1144 - 1144

Published: July 3, 2024

Huntington’s disease (HD) is a rare but progressive and devastating neurodegenerative characterized by involuntary movements, cognitive decline, executive dysfunction, neuropsychiatric conditions such as anxiety depression. It follows an autosomal dominant inheritance pattern. Thus, child who has parent with the mutated huntingtin (mHTT) gene 50% chance of developing disease. Since HTT protein involved in many critical cellular processes, including neurogenesis, brain development, energy metabolism, transcriptional regulation, synaptic activity, vesicle trafficking, cell signaling, autophagy, its aberrant aggregates lead to disruption numerous pathways neurodegeneration. Essential heavy metals are vital at low concentrations; however, higher concentrations, they can exacerbate HD disrupting glial–neuronal communication and/or causing dysbiosis (disturbance gut microbiota, GM), both which neuroinflammation further Here, we discuss detail interactions iron, manganese, copper glial–neuron GM indicate how this knowledge may pave way for development new generation disease-modifying therapies HD.

Language: Английский

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Role of Glial Cells and Receptors in Schizophrenia Pathogenesis

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(2)

Published: Jan. 27, 2025

Language: Английский

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Neuron identity switches in response to the gradient gene expression pathway

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: Feb. 19, 2025

Nonstatic Neuron identity emerges from the complementary synaptic transcriptional architecture shaped by neuron signaling and surrounding non-neuronal cells. When signals a series of neurons are combined, they form circuits through which information flows, brain functioning occurs as superposition these neural circuits. To ensure proper communication function, develop phenotypes axonal projections electrophysiological behaviors, creating gradients that define regions allocate neurochemical functions (Vogel et al., 2024).In mature nervous system, extend over long distances communicate with different well-established (Pal 2024) in both peripheral systems (PNS) central (CNS). Information flows inside each axon despite great distance, resulting immediate responses.The mechanism involved response has been described. The soma-centric notion is main idea for this mechanism, where neuronal soma provides total molecular (Dalla Costa 2021). However, Nijssen (2018) showed evidence differences between transcriptome Spinal Motor Neurons (MNs).Several authors suggest that, given differences, alone may not provide all transcriptomic information. Instead, glial cells accompanying along its pathway supply some These play an essential role function. 2021;Giuditta 2008).The described glia-to-axon relationship becomes particularly significant CNS, have distinct molecular, cellular, functional characteristics 2024;Siletti 2023). As axons various areas, their profiles differ soma's (Nijssen 2018). This variation suggests adapt to match local cellular environment traverse regions. specific resources area. We term space-dependent, dynamic adaptation "neuronal continuum."Modern neuroscience produced high-resolution cell classifications based on expression single-cell sequencing techniques such Single-Nucleus RNA (snRNA-seq) (Siletti technique focuses nuclei (Hodge 2019). atlases us CNS cartography most species 2023;Yao 2023;Chen 2023), typically report two groups neurons-glutamatergic GABAergic-together third lineage known glia, plays critical regulatory roles throughout (Liu 2023).Different cognitive region-associated require configurations axondendrite junctions 2021), determine how flows. physical pathways, dendrite morphology can change, crucial communication.Recent research shown changes often accompany regulation gene (Gao (2018), developed method single axon, similar snRNA-seq, called Axon-seq. They sequenced MNs, finding profile differs neuron. More interestingly, unique transcription factor signature was found distal any reported, leading questions: Who responsible switch, why does happen?Glial constitute half population mammalian system. glia-toneuron ratio varies across structures classified into types: astrocytes, microglia, synantocytes (Tizabi 2024), oligodendrocytes Schwann cells, last being myelin Similar scenarios exist PNS maintain close relationship. Glial residing at or within segments providing fundamental support survival 2023).Recent findings highlighted contribution show shifting sheaths (Xin Chan, 2020). also very diverse, varying subtypes proportions neighborhoods regions; neighborhood own types glia Giuditta (2008) mechanisms direct squid giant showing beyond simple soma/axon, content axon. Studies reported interact deliver genetic material machinery (Das Court demonstrated flow ribosomes Furthermore, recently other explained axons, describing exosome (cargo information) exchange oligodendrocyte-to-axonBesides neurons, reach up meter humans (Twiss Fainzilber, 2009), travel layers brain. frontotemporal arcuate fasciculus (AF) well-studied connects white matter bundle language processing 4-5 cm (Basile 2024).Despite delivery primary proposed mRNA transport Twiss (2009) anterograde rate only 16 mm/hour, suggesting relying solely nuclear synthesis insufficient due retrograde needed travel. observations highlight limitations nucleus axons.Gene were initially rostral-caudal direction (Fornito Lau (2021) shows gradual decay according distance mouse cortex. Vogel (2024), three principal axes aligned brain's anatomical architecture.In addition, snRNA-seq studies continuity major populations adult human brains 2023;Hodge 2019), type region.Current explores multiple scales (micro-meso-macro scales), defined informational unit. For example, mesoscale, unit would be set neighboring locally expression. From shared expression, emerge, i.e. morphology, interconnectivity (Poulin 2016). Each fuzzily self-defined space brain, will those boundaries shift dynamically microgradients. Individual whose cross sources thrive.Since scales, it plausible phenomenon individual neurons. region molecularly, cellularly, functionally patterns necessary cerebral function.While distances, visit change segment acquires soma, combining one supplied (Farias Such continuum means do but continuous collectively established dependent (Fig. 1).We propose oligodendrocytes, secondarily serve glia-to-axon, compartments PNS. Recent demonstrate regulating synapse development, transmission, plasticity 2023;Xin 2020).The impacts myelin-associated diseases disorders. compared healthy amyotrophic lateral sclerosis demonstrating differential 121 mRNAs property Also, oligodendrocyte heterogeneity implicated conditions Multiple Sclerosis.In typical demyelination disease, control patients could contribute inflammation (Jäkel possibly disruption certain derived missing subtypes. myelin-related impact commonly associated disorders (Murdock Tsai, By acknowledging spatially resources, we better understand complex interplay health disease.The traditional view possessing fixed intrinsic properties challenged emerging continuum. Figure 1. compartment switches function location moves, resembling neighborhood. A) distinct. B) Axonal pathways longer. connecting C) At beginning path, body begins pathway. On way, accompanied (and cells), maintained. D) Due relationship, occurs, where, transfer (Krämer-Albers Werner, segment, depends located. Giving rise proteins combined coming produces switch E) end pathway, compartments, non-static space-dependent "Neuronal Continuum."

Language: Английский

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Role of glial cells in neurotoxicological effects of alcohol

Advances in neurotoxicology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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The role of strial macrophages in the maintenance of the blood–labyrinth barrier

Academia Biology, Journal Year: 2025, Volume and Issue: 3(2)

Published: April 16, 2025

Macrophages in the cochlear stria vascularis (SV) are crucial for maintaining integrity of blood–labyrinth barrier (BLB) and supporting auditory function. Using a macrophage depletion mouse model during development, we conducted comprehensive series assessments to elucidate role strial macrophages BLB. These included brainstem response tests, flow cytometry, immunofluorescence staining, immunoblotting, permeability assays on postnatal day 35. We found that SV led increased BLB high-frequency hearing loss, which were accompanied by decreased vessel density, reduced branching index, loss tight junctions. findings highlight essential formation fully functional BLB, providing new insights into sensorineural particularly compartment.

Language: Английский

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The Gut Microbiome-Neuroglia Axis: Implications for Brain Health, Inflammation, and Disease

Neuroglia, Journal Year: 2024, Volume and Issue: 5(3), P. 254 - 273

Published: Aug. 1, 2024

The human central nervous system is convolutedly connected to the gut microbiome, a diverse community of microorganisms residing in gastrointestinal tract. Recent research has highlighted bidirectional communication between microbiome and neuroglial cells, which include astrocytes, microglia, oligodendrocytes, ependymal cells. These cells are essential for maintaining CNS homeostasis, supporting neuronal function, responding pathological conditions. This review examines interactions neuroglia, emphasizing their critical roles brain health development neurological disorders. Dysbiosis, or imbalance been associated with various psychiatric conditions, such as autism spectrum disorder, anxiety, depression, neurodegenerative diseases like Alzheimer’s Parkinson’s. influences function through microbial metabolites, immune modulation, neuroinflammatory responses. Understanding these paves way new therapeutic targets strategies preventing treating scoping aims highlight mechanisms microbiome-neuroglia axis its potential target.

Language: Английский

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Translating Molecular Approaches to Oligodendrocyte-Mediated Neurological Circuit Modulation

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(7), P. 648 - 648

Published: June 27, 2024

The central nervous system (CNS) exhibits remarkable adaptability throughout life, enabled by intricate interactions between neurons and glial cells, in particular, oligodendrocytes (OLs) oligodendrocyte precursor cells (OPCs). This is pivotal for learning memory, with OLs OPCs playing a crucial role neural circuit development, synaptic modulation, myelination dynamics. Myelination not only supports axonal conduction but also undergoes adaptive modifications response to neuronal activity, which vital cognitive processing memory functions. review discusses how these cellular myelin dynamics are implicated various neurocircuit diseases disorders such as epilepsy, gliomas, psychiatric conditions, focusing on maladaptive changes contribute disease pathology influence clinical outcomes. It covers the potential new diagnostics therapeutic approaches, including pharmacological strategies emerging biomarkers functions processes. evidence fundamental plasticity functionality synchronizing activity high-level functions, offering promising avenues targeted interventions CNS disorders.

Language: Английский

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Intercellular Adhesion Molecule 1 (ICAM-1): An Inflammatory Regulator with Potential Implications in Ferroptosis and Parkinson’s Disease

Cells, Journal Year: 2024, Volume and Issue: 13(18), P. 1554 - 1554

Published: Sept. 15, 2024

Intercellular adhesion molecule 1 (ICAM-1/CD54), a transmembrane glycoprotein, has been considered as one of the most important molecules during leukocyte recruitment. It is encoded by ICAM1 gene and plays central role in inflammation. Its crucial many inflammatory diseases such ulcerative colitis rheumatoid arthritis are well established. Given that neuroinflammation, underscored microglial activation, key element neurodegenerative Parkinson’s disease (PD), we investigated whether ICAM-1 this progressive neurological condition and, if so, to elucidate underpinning mechanisms. Specifically, were interested potential interaction between ICAM-1, glial cells, ferroptosis, an iron-dependent form cell death recently implicated PD. We conclude there exist direct indirect (via cells T cells) influences on ferroptosis further elucidation these interactions can suggest novel intervention for devastating disease.

Language: Английский

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Heavy Metals Interactions with Neuroglia and Gut Microbiota: Implications for Huntington’s Disease

Published: June 12, 2024

Huntington’s disease (HD) is a rare but progressive and devastating neurodegenerative characterized by involuntary movements, cognitive decline, executive dysfunction, neuropsychiatric conditions such as anxiety depression. It follows an autosomal dominant inheritance pattern. Thus, child who has parent with the mutated huntingtin (mHTT) gene 50% chance of developing disease. Since HTT protein involved in many critical cellular processes including neurogenesis, brain development, energy metabolism, transcriptional regulation, synaptic activity, vesicle trafficking, cell signaling, autophagy, its aberrant aggregates lead to disruption numerous pathways neurodegeneration. Essential heavy metals are vital at low concentrations, however, higher can exacerbate HD disrupting glial-neuronal communication, and/or causing dysbiosis (disturbance gut microbiota, GM), both which neuroinflammation further Here, we discuss detail interactions iron, manganese copper glial-neuron communication GM indicate how this knowledge may pave way for development new generation disease-modifying therapies HD.

Language: Английский

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