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Cell Reports Jun 2024Alcohol is the most widely used addictive substance, potentially leading to brain damage and genetic abnormalities. Despite its prevalence and associated risks, current...
Alcohol is the most widely used addictive substance, potentially leading to brain damage and genetic abnormalities. Despite its prevalence and associated risks, current treatments have yet to identify effective methods for reducing cravings and preventing relapse. In this study, we find that 4-Hz alternating bilateral sensory stimulation (ABS) effectively reduces ethanol-induced conditioned place preference (CPP) in male mice, while 4-Hz flash light does not exhibit therapeutic effects. Whole-brain c-Fos mapping demonstrates that 4-Hz ABS triggers notable activation in superior colliculus GABAergic neurons (SC). SC forms monosynaptic connections with ventral tegmental area dopaminergic neurons (VTA), which is implicated in ethanol-induced CPP. Bidirectional chemogenetic manipulation of SC-VTA circuit either replicates or blocks the therapeutic effects of 4-Hz ABS on ethanol-induced CPP. These findings elucidate the role of SC-VTA circuit for alleviating ethanol-related CPP by 4-Hz ABS and point to a non-drug and non-invasive approach that might have potential for treating alcohol use disorder.
PubMed: 38923461
DOI: 10.1016/j.celrep.2024.114383 -
Headache Jun 2024To identify the most common locations of cluster headache pain from an international, non-clinic-based survey of participants with cluster headache, and to compare these...
OBJECTIVE
To identify the most common locations of cluster headache pain from an international, non-clinic-based survey of participants with cluster headache, and to compare these locations to other cluster headache features as well as to somatotopic maps of peripheral, brainstem, thalamic, and cortical areas.
BACKGROUND
Official criteria for cluster headache state pain in the orbital, supraorbital, and/or temporal areas, yet studies have noted pain extending beyond these locations, and the occipital nerve appears relevant, given the effectiveness of suboccipital corticosteroid injections and occipital nerve stimulation. Furthermore, cranial autonomic features vary between patients, and it is not clear if the trigeminovascular reflex is dermatome specific (e.g., do patients with maxillary or V2 division pain have more rhinorrhea?). Finally, functional imaging studies show early activation of the posterior hypothalamus in a cluster headache attack. However, the first somatosensory area to be sensitized is unclear; the first area can be hypothesized based on the complete map of pain locations.
METHODS
The International Cluster Headache Questionnaire was an internet-based cross-sectional survey that included a clickable pain map of the face. These data were compared to several other datasets: (1) a meta-analysis of 22 previous publications of pain location in cluster headache (consisting of 6074 patients); (2) four cephalic dermatome maps; (3) participants' survey responses for demographics, autonomic features, and effective medications; and (4) previously published somatotopic maps of the brainstem, thalamus, primary somatosensory cortex, and higher order somatosensory cortex.
RESULTS
One thousand five hundred eighty-nine participants completed the pain map portion of the survey, and the primary locations of pain across all respondents was the orbital, periorbital, and temporal areas with a secondary location in the lower occiput; these primary and secondary locations were consistent with our meta-analysis of 22 previous publications. Of the four cephalic dermatomes (V1, V2, V3, and a combination of C2-3), our study found that most respondents had pain in two or more dermatomes (range 85.7% to 88.7%, or 1361-1410 of 1589 respondents, across the four dermatome maps). Dermatomes did not correlate with their respective autonomic features or with medication effectiveness. The first area to be sensitized in the canonical somatosensory pathway is either a subcortical (brainstem or thalamus) or higher order somatosensory area (parietal ventral or secondary somatosensory cortices) because the primary somatosensory cortex (area 3b) and somatosensory area 1 have discontinuous face and occipital regions.
CONCLUSIONS
The primary pain locations in cluster headache are the orbital, supraorbital, and temporal areas, consistent with the official International Classification of Headache Disorders criteria. However, activation of the occiput in many participants suggests a role for the occipital nerve, and the pain locations suggest that somatosensory sensitization does not start in the primary somatosensory cortex.
PubMed: 38922887
DOI: 10.1111/head.14766 -
Molecular Biology of the Cell Jun 2024Contractile myosin and cell adhesion work together to induce tissue shape changes, but how they are patterned to achieve diverse morphogenetic outcomes remains unclear....
Contractile myosin and cell adhesion work together to induce tissue shape changes, but how they are patterned to achieve diverse morphogenetic outcomes remains unclear. Epithelial folding occurs via apical constriction, mediated by apical contractile myosin engaged with adherens junctions, as in Drosophila ventral furrow formation. While it has been shown that a multicellular gradient of myosin contractility determines folding shape, the impact of multicellular patterning of adherens junction levels on tissue folding is unknown. We identified a novel Drosophila gene essential for differential apical constriction and folding behaviors across the ventral epithelium which contains both folding ventral furrow and non-folding ectodermal anterior midgut (ectoAMG). We show that Moat functions to downregulate polarity-dependent adherens junctions through inhibiting cortical clustering of Bazooka/Par3 proteins. Such downregulation of polarity-dependent junctions is critical for establishing a myosin-dependent pattern of adherens junctions, which in turn mediates differential apical constriction in the ventral epithelium. In mutants, abnormally high levels of polarity-dependent junctions promote ectopic apical constriction in cells with low-level contractile myosin, resulting in expansion of infolding from ventral furrow to ectoAMG, and flattening of ventral furrow constriction gradient. Our results demonstrate that tissue-scale distribution of adhesion levels patterns apical constriction and establishes morphogenetic boundaries. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].
PubMed: 38922850
DOI: 10.1091/mbc.E24-04-0177 -
Hernia : the Journal of Hernias and... Jun 2024Robot-assisted ventral hernia repair is associated with decreased length of stay and lower complication rates compared with open repair, but acquisition and maintenance...
BACKGROUND
Robot-assisted ventral hernia repair is associated with decreased length of stay and lower complication rates compared with open repair, but acquisition and maintenance of the robotic system is costly. The aim of this was study was to compare the procedure-specific cost of robot-assisted and open ventral and incisional hernia repair including cost of procedure-related readmissions and reoperations within 90 days postoperatively.
METHODS
Single-center retrospective cohort study of 100 patients undergoing robot-assisted ventral hernia. Patients were propensity-score matched 1:1 with 100 patients undergoing open repairs on age, type of hernia (primary/incisional), and horizontal defect size. The primary outcome of the study was the total cost per procedure in Euros including the cost of a robotic approach, extra ports, mesh, tackers, length of stay, length of readmission, and operative reintervention. The cost of the robot itself was not included in the cost calculation.
RESULTS
The mean length of stay was 0.3 days for patients undergoing robot-assisted ventral hernia repair, which was significantly shorter compared with 2.1 days for patients undergoing open repair, P < 0.005. The readmission rate was 4% for patients undergoing robot-assisted ventral hernia repairs and was significantly lower compared with open repairs (17%), P = 0.006. The mean total cost of all robot-assisted ventral and incisional hernia repairs was 1,094 euro compared with 1,483 euro for open repairs, P = 0.123. The total cost of a robot-assisted incisional hernia repair was significantly lower (1,134 euros) compared with open ventral hernia repair (2,169 euros), P = 0.005.
CONCLUSIONS
In a Danish cohort of patients with incisional hernia, robot-assisted incisional hernia repair was more cost-effective than an open repair due to shortened length of stay, and lower rates of readmission and reintervention within 90 days.
PubMed: 38922513
DOI: 10.1007/s10029-024-03089-7 -
Veterinary Sciences Jun 2024A two-year-old female crossbreed dog, previously a stray with no known owner, was adopted and subsequently spayed. The dog exhibited weight loss over a period of two...
A two-year-old female crossbreed dog, previously a stray with no known owner, was adopted and subsequently spayed. The dog exhibited weight loss over a period of two months and died suddenly during a leashed walk. Upon necropsy, enlargement of the submandibular, prescapular, and popliteal lymph nodes was noted. The intrathoracic cavity contained a substantial volume of yellowish-white fluid. Lymph nodes in the mediastinal and ventral thoracic centers were also enlarged, hemorrhagic, and friable. Microscopic examination revealed significant architectural changes in the lymph nodes, characterized by a pronounced cellular infiltrate consisting of lymphocytes and histiocytes, along with macrophages containing intracytoplasmic amastigotes. Immunohistochemical analysis of the lymph nodes confirmed positive staining for amastigotes. This case represents the first report of canine leishmaniasis associated with acute pleural effusion and sudden death.
PubMed: 38922000
DOI: 10.3390/vetsci11060254 -
Cells Jun 2024Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration in the central nervous system. Recent research has...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration in the central nervous system. Recent research has increasingly linked the activation of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome to ALS pathogenesis. NLRP3 activation triggers Caspase 1 (CASP 1) auto-activation, leading to the cleavage of Gasdermin D (GSDMD) and pore formation on the cellular membrane. This process facilitates cytokine secretion and ultimately results in pyroptotic cell death, highlighting the complex interplay of inflammation and neurodegeneration in ALS. This study aimed to characterize the NLRP3 inflammasome components and their colocalization with cellular markers using the wobbler mouse as an ALS animal model. Firstly, we checked the levels of miR-223-3p because of its association with NLRP3 inflammasome activity. The wobbler mice showed an increased expression of miR-223-3p in the ventral horn, spinal cord, and cerebellum tissues. Next, increased levels of NLRP3, pro-CASP 1, cleaved CASP 1 (c-CASP 1), full-length GSDMD, and cleaved GDSMD revealed NLRP3 inflammasome activation in wobbler spinal cords, but not in the cerebellum. Furthermore, we investigated the colocalization of the aforementioned proteins with neurons, microglia, and astrocyte markers in the spinal cord tissue. Evidently, the wobbler mice displayed microgliosis, astrogliosis, and motor neuron degeneration in this tissue. Additionally, we showed the upregulation of protein levels and the colocalization of NLRP3, c-CASP1, and GSDMD in neurons, as well as in microglia and astrocytes. Overall, this study demonstrated the involvement of NLRP3 inflammasome activation and pyroptotic cell death in the spinal cord tissue of wobbler mice, which could further exacerbate the motor neuron degeneration and neuroinflammation in this ALS mouse model.
Topics: Animals; Amyotrophic Lateral Sclerosis; NLR Family, Pyrin Domain-Containing 3 Protein; Motor Neurons; Inflammasomes; Mice; MicroRNAs; Spinal Cord; Disease Models, Animal; Nerve Degeneration; Microglia; Mice, Inbred C57BL; Caspase 1
PubMed: 38920626
DOI: 10.3390/cells13120995 -
Medical Review (2021) Jun 2024Mammalian lung development starts from a specific cluster of endodermal cells situated within the ventral foregut region. With the orchestrating of delicate choreography... (Review)
Review
Mammalian lung development starts from a specific cluster of endodermal cells situated within the ventral foregut region. With the orchestrating of delicate choreography of transcription factors, signaling pathways, and cell-cell communications, the endodermal diverticulum extends into the surrounding mesenchyme, and builds the cellular and structural basis of the complex respiratory system. This review provides a comprehensive overview of the current molecular insights of mammalian lung development, with a particular focus on the early stage of lung cell fate differentiation and spatial patterning. Furthermore, we explore the implications of several congenital respiratory diseases and the relevance to early organogenesis. Finally, we summarize the unprecedented knowledge concerning lung cell compositions, regulatory networks as well as the promising prospect for gaining an unbiased understanding of lung development and lung malformations through state-of-the-art single-cell omics.
PubMed: 38919401
DOI: 10.1515/mr-2023-0064 -
Nature Communications Jun 2024Nociceptin/orphanin-FQ (N/OFQ) is a recently appreciated critical opioid peptide with key regulatory functions in several central behavioral processes including...
Nociceptin/orphanin-FQ (N/OFQ) is a recently appreciated critical opioid peptide with key regulatory functions in several central behavioral processes including motivation, stress, feeding, and sleep. The functional relevance of N/OFQ action in the mammalian brain remains unclear due to a lack of high-resolution approaches to detect this neuropeptide with appropriate spatial and temporal resolution. Here we develop and characterize NOPLight, a genetically encoded sensor that sensitively reports changes in endogenous N/OFQ release. We characterized the affinity, pharmacological profile, spectral properties, kinetics, ligand selectivity, and potential interaction with intracellular signal transducers of NOPLight in vitro. Its functionality was established in acute brain slices by exogeneous N/OFQ application and chemogenetic induction of endogenous N/OFQ release from PNOC neurons. In vivo studies with fibre photometry enabled direct recording of NOPLight binding to exogenous N/OFQ receptor ligands, as well as detection of endogenous N/OFQ release within the paranigral ventral tegmental area (pnVTA) during natural behaviors and chemogenetic activation of PNOC neurons. In summary, we show here that NOPLight can be used to detect N/OFQ opioid peptide signal dynamics in tissue and freely behaving animals.
Topics: Animals; Opioid Peptides; Nociceptin; Receptors, Opioid; Neurons; Humans; Mice; Male; Ventral Tegmental Area; Nociceptin Receptor; HEK293 Cells; Brain; Mice, Inbred C57BL; Ligands; Biosensing Techniques
PubMed: 38918403
DOI: 10.1038/s41467-024-49712-0 -
ENeuro Jun 2024The zebrafish, a widely used model in neurobiology, relies on hearing in aquatic environments. Unfortunately, its auditory pathways have mainly been studied in larvae....
The zebrafish, a widely used model in neurobiology, relies on hearing in aquatic environments. Unfortunately, its auditory pathways have mainly been studied in larvae. In this study, we examined the involvement of the anterior tuberal nucleus (AT) in auditory processing in adult zebrafish. Our tract-tracing experiments revealed that the dorsal subdivision of AT is strongly bidirectionally connected to the central nucleus of the torus semicircularis (TSc), a major auditory nucleus in fishes. Immunohistochemical visualisation of the ribosomal protein S6 (pS6) phosphorylation to map neural activity in response to auditory stimulation substantiated this finding: the dorsal but not the ventral part of AT responded strongly to auditory stimulation. A similar response to auditory stimulation was present in the TSc but not in the nucleus isthmi (NI), a visual region, which we used as a control for testing if the pS6 activation was specific to the auditory stimulation. We also measured the time course of pS6 phosphorylation, which was previously unreported in teleost fish. After auditory stimulation, we found that pS6 phosphorylation peaked between 100-130 minutes and returned to baseline levels after 190 minutes. This information will be valuable for the design of future pS6 experiments. Our results suggest an anatomical and functional subdivision of AT, where only the dorsal part connects to the auditory network and processes auditory information. We investigated the involvement of the anterior tuberal nucleus in zebrafish in auditory processing. Our study revealed a functional and anatomical subdivision of this region. We show that its dorsal subdivision is strongly connected to the central nucleus of the torus semicircularis, a major auditory nucleus in fishes. pS6 phosphorylation, as an indirect marker of neuronal activity after auditory stimulation, substantiated that only the dorsal anterior tuberal nucleus, processes auditory information. We also show that after auditory stimulation, pS6 phosphorylation peaked between 100-130 minutes and returned to baseline levels after 190 minutes, providing valuable information for future studies.
PubMed: 38918052
DOI: 10.1523/ENEURO.0062-24.2024 -
Biomedicine & Pharmacotherapy =... Jun 20245-HT clearance, commonly mediated by transporters in the uptake-1 and uptake-2 families, has been linked to 5-HT receptor's action on behaviors. Since no specific...
5-HT clearance, commonly mediated by transporters in the uptake-1 and uptake-2 families, has been linked to 5-HT receptor's action on behaviors. Since no specific transporters identified yet, effects of serotonin transporter (SERT) and organic cation transporter (OCTs) on 5-HT-elicited immobility phenotype, and 5-HT and HIS uptake were then investigated. Intraperitoneal injections of SERT inhibitor fluoxetine (FLX) and/or OCTs inhibitor decynium (D22) were used prior to local perfusion of 5-HT agonist CP93129 into the ventral hippocampus to measure immobility times in the FST and TST, to measure 5-HT uptake efficiencies and HIS uptake efficiencies derived from linear regressions using the transient no-net-flux quantitative microdialysis in C57BL/6 mice. Exogenous 5-HT and HIS uptake were measured following incubation of FLX and/or D22 with CP93129 in the RBL-2H3 cells. Moreover, surface membrane levels of SERT and OCT were detected in response to CP93129. Local CP93129 prolonged immobility times, which were attenuated following pretreatment of either inhibitor. Local CP93129 lowered the slopes obtained from the lineal regressions for 5-HT and HIS (slope is reciprocal to uptake efficiency), which were then weakened following pretreatment of either inhibitor. Similar findings were obtained following CP93129 incubation, and co-incubation of CP93129 with either inhibitor in the RBL-2H3. Moreover, CP93129 dose-dependently moved SERT and OCT3 in the cytosol to the surface membrane. Both SERT and OCT are the target effectors mediating 5-HT regulation of immobility time and 5-HT uptake, OCT mediates 5-HT regulation of HIS uptake. Their underlying signal transductions need to be further explored.
PubMed: 38917762
DOI: 10.1016/j.biopha.2024.117017