keyword
https://read.qxmd.com/read/38535458/using-constellation-pharmacology-to-characterize-a-novel-%C3%AE-conotoxin-from-conus-ateralbus
#1
JOURNAL ARTICLE
Jorge L B Neves, Cristoval Urcino, Kevin Chase, Cheryl Dowell, Arik J Hone, David Morgenstern, Victor M Chua, Iris Bea L Ramiro, Julita S Imperial, Lee S Leavitt, Jasmine Phan, Fernando A Fisher, Maren Watkins, Shrinivasan Raghuraman, Jortan O Tun, Beatrix M Ueberheide, J Michael McIntosh, Vitor Vasconcelos, Baldomero M Olivera, Joanna Gajewiak
The venom of cone snails has been proven to be a rich source of bioactive peptides that target a variety of ion channels and receptors. α-Conotoxins (αCtx) interact with nicotinic acetylcholine receptors (nAChRs) and are powerful tools for investigating the structure and function of the various nAChR subtypes. By studying how conotoxins interact with nAChRs, we can improve our understanding of these receptors, leading to new insights into neurological diseases associated with nAChRs. Here, we describe the discovery and characterization of a novel conotoxin from Conus ateralbus , αCtx-AtIA, which has an amino acid sequence homologous to the well-described αCtx-PeIA, but with a different selectivity profile towards nAChRs...
February 29, 2024: Marine Drugs
https://read.qxmd.com/read/38531262/trpv1-receptor-structure-activation-modulation-and-role-in-neuro-immune-interactions-and-pain
#2
REVIEW
Thaila Kawane Euflazio Maximiano, Jessica Aparecida Carneiro, Victor Fattori, Waldiceu A Verri
In the 1990s, the identification of a non-selective ion channel, especially responsive to capsaicin, revolutionized the studies of somatosensation and pain that were to follow. The TRPV1 channel is expressed mainly in neuronal cells, more specifically, in sensory neurons responsible for the perception of noxious stimuli. However, its presence has also been detected in other non-neuronal cells, such as immune cells, β- pancreatic cells, muscle cells and adipocytes. Activation of the channel occurs in response to a wide range of stimuli, such as noxious heat, low pH, gasses, toxins, endocannabinoids, lipid-derived endovanilloid, and chemical agents, such as capsaicin and resiniferatoxin...
March 8, 2024: Cell Calcium
https://read.qxmd.com/read/38531121/a-next-generation-peripherally-restricted-cav%C3%AE-2%C3%AE-1-ligand-with-inhibitory-action-on-cav2-2-channels-and-utility-in-neuropathic-pain
#3
JOURNAL ARTICLE
Franz Kricek, Christine Ruf, Premji Meghani, Ivana A Souza, Maria A Gandini, Gerald W Zamponi, George Skouteris
The Voltage-Gated Calcium Channel (VGCC) auxiliary subunit Cavα2δ-1 (CACNA2D1) is the target/receptor of gabapentinoids which are known therapeutics in epilepsy and neuropathic pain. Following damage to the peripheral sensory nervous system, Cavα2δ-1 is upregulated in dorsal root ganglion (DRG) neurons in several animal models of chronic neuropathic pain. Gabapentinoids, such as gabapentin and pregabalin, engage with Cavα2δ-1 via binding an arginine residue (R241) within an RRR motif located at the N-terminus of human Cavα2δ-1...
March 25, 2024: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/38530893/feedforward-and-feedback-mechanisms-cooperatively-regulate-rapid-experience-dependent-response-adaptation-in-a-single-thermosensory-neuron-type
#4
JOURNAL ARTICLE
Tyler J Hill, Piali Sengupta
Sensory adaptation allows neurons to adjust their sensitivity and responses based on recent experience. The mechanisms that mediate continuous adaptation to stimulus history over seconds- to hours-long timescales, and whether these mechanisms can operate within a single sensory neuron type, are unclear. The single pair of AFD thermosensory neurons in Caenorhabditis elegans exhibits experience-dependent plasticity in their temperature response thresholds on both minutes- and hours-long timescales upon a temperature upshift...
April 2, 2024: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/38526284/cav3-2-channel-regulates-cerebral-ischemia-reperfusion-injury-a-promising-target-for-intervention
#5
JOURNAL ARTICLE
Feibiao Dai, Chengyun Hu, Xue Li, Zhetao Zhang, Hongtao Wang, Wanjun Zhou, Jiawu Wang, Qingtian Geng, Yongfei Dong, Chaoliang Tang
JOURNAL/nrgr/04.03/01300535-202419110-00028/figure1/v/2024-03-08T184507Z/r/image-tiff Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury. Various calcium channels are involved in cerebral ischemia/reperfusion injury. Cav3.2 channel is a main subtype of T-type calcium channels. T-type calcium channel blockers, such as pimozide and mibefradil, have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury. However, the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear...
November 1, 2024: Neural Regeneration Research
https://read.qxmd.com/read/38522401/calcium-induced-upregulation-of-energy-metabolism-heats-neurons-during-neural-activity
#6
JOURNAL ARTICLE
Jiayang Wu, Yutaka Shindo, Kohji Hotta, Cong Quang Vu, Kai Lu, Tetsuichi Wazawa, Takeharu Nagai, Kotaro Oka
Cellular temperature affects every biochemical reaction, underscoring its critical role in cellular functions. In neurons, temperature not only modulates neurotransmission but is also a key determinant of neurodegenerative diseases. Considering that the brain consumes a disproportionately high amount of energy relative to its weight, neural circuits likely generate a lot of heat, which can increase cytosolic temperature. However, the changes in temperature within neurons and the mechanisms of heat generation during neural excitation remain unclear...
March 22, 2024: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/38517838/see-elegans-simple-to-use-accurate-and-automatic-3d-detection-of-neural-activity-from-densely-packed-neurons
#7
JOURNAL ARTICLE
Enrico Lanza, Valeria Lucente, Martina Nicoletti, Silvia Schwartz, Ilaria F Cavallo, Davide Caprini, Christopher W Connor, Mashel Fatema A Saifuddin, Julia M Miller, Noelle D L'Etoile, Viola Folli
In the emerging field of whole-brain imaging at single-cell resolution, which represents one of the new frontiers to investigate the link between brain activity and behavior, the nematode Caenorhabditis elegans offers one of the most characterized models for systems neuroscience. Whole-brain recordings consist of 3D time series of volumes that need to be processed to obtain neuronal traces. Current solutions for this task are either computationally demanding or limited to specific acquisition setups. Here, we propose See Elegans, a direct programming algorithm that combines different techniques for automatic neuron segmentation and tracking without the need for the RFP channel, and we compare it with other available algorithms...
2024: PloS One
https://read.qxmd.com/read/38516585/inhibition-of-n-type-calcium-channels-by-phenoxyaniline-and-sulfonamide-analogues
#8
JOURNAL ARTICLE
Anjie S Bispat, Fernanda C Cardoso, Md Mahadhi Hasan, Yashad Dongol, Ricki Wilcox, Richard J Lewis, Peter J Duggan, Kellie L Tuck
Building on previous investigations, structural modifications to the neuronal calcium ion channel blocker MONIRO-1 and related compounds were conducted that included replacement of the amide linker with an aniline and isosteric sulfonamide moiety, and the previously used strategy of substitution of the guanidinium group with less hydrophilic amine functionalities. A comprehensive SAR study revealed a number of phenoxyaniline and sulfonamide compounds that were more potent or had similar potency for the CaV 2...
March 20, 2024: RSC medicinal chemistry
https://read.qxmd.com/read/38514804/the-alzheimer-s-disease-risk-gene-bin1-regulates-activity-dependent-gene-expression-in-human-induced-glutamatergic-neurons
#9
JOURNAL ARTICLE
Orthis Saha, Ana Raquel Melo de Farias, Alexandre Pelletier, Dolores Siedlecki-Wullich, Bruna Soares Landeira, Johanna Gadaut, Arnaud Carrier, Anaïs-Camille Vreulx, Karine Guyot, Yun Shen, Amelie Bonnefond, Philippe Amouyel, Julia Tcw, Devrim Kilinc, Claudio Marcos Queiroz, Fabien Delahaye, Jean-Charles Lambert, Marcos R Costa
Bridging Integrator 1 (BIN1) is the second most important Alzheimer's disease (AD) risk gene, but its physiological roles in neurons and its contribution to brain pathology remain largely elusive. In this work, we show that BIN1 plays a critical role in the regulation of calcium homeostasis, electrical activity, and gene expression of glutamatergic neurons. Using single-cell RNA-sequencing on cerebral organoids generated from isogenic BIN1 wild type (WT), heterozygous (HET) and homozygous knockout (KO) human-induced pluripotent stem cells (hiPSCs), we show that BIN1 is mainly expressed by oligodendrocytes and glutamatergic neurons, like in the human brain...
March 22, 2024: Molecular Psychiatry
https://read.qxmd.com/read/38513594/tolperisone-hydrochloride-improves-motor-functions-in-parkinson-s-disease-via-mmp-9-inhibition-and-by-downregulating-p38-mapk-and-erk1-2-signaling-cascade
#10
JOURNAL ARTICLE
Bushra Zaman, Irona Mostafa, Tazree Hassan, Shamim Ahmed, Nusrat Jahan Ikbal Esha, Fowzia Afsana Chowdhury, Tory Bosu, Humayra Noor Chowdhury, Anup Mallick, Mm Shanjid Islam, Ayesha Sharmin, Kabir M Uddin, Md Mainul Hossain, Mahbubur Rahman
The mitogen-activated protein kinase (MAPK) signaling pathway, particularly the p38 MAPK and ERK1/2, has been implicated in the pathogenesis of Parkinson's disease (PD). Recent studies have shown that MAPK signaling pathway can influence the expression of matrix metalloproteinase 9 (MMP-9), known for its involvement in various physiological and pathological processes, including neurodegenerative diseases. This study explores the modulation of MMP-9 expression via the MAPK/ERK signaling cascade and its potential therapeutic implications in the context of PD-associated motor dysfunction...
March 20, 2024: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/38502673/bk-zero-isoform-hek293-stably-transfected-cell-lines-differing-3-utrs-to-assess-mir-9-regulation
#11
JOURNAL ARTICLE
Katherine Cordero Padilla, Gerardo Alvarado Monefeldt, Adriel Guevárez Galán, Hector G Marrero, Mario E Lloret-Torres, Cristina Velázquez-Marrero
Research has identified the large conductance voltage- and calcium-activated potassium channel (BK) as a key regulator of neuronal excitability genetically associated to behavioral alcohol tolerance. Sensitivity to ethanol at the molecular level is characterized by acute potentiation of channel activity. BK isoforms show variations in alcohol sensitivity and are differentially distributed on the plasma membrane surface in response to prolonged exposure. MicroRNA (MiRNA) targeting of alcohol-sensitive isoforms coupled with active internalization of BK channels in response to ethanol are believed to be key in establishing homeostatic adaptations that produce persistent changes within the plasma membrane of neurons...
2024: PloS One
https://read.qxmd.com/read/38500328/progress-of-researches-on-mechanisms-of-acupuncture-underlying-improvement-of-cerebral-ischemia-reperfusion-injury-by-regulating-calcium-overload
#12
JOURNAL ARTICLE
Chan-Juan Liu, Peng Sang
Ischemic stroke is currently the most common type of stroke, and the key pathological link is cerebral ischemia-reperfusion injury (CIRI), while the key factor leading to apoptosis and necrosis of ischemic nerve cells is calcium overload. Current studies have confirmed that acupuncture therapy has a good modulating effect on calcium homeostasis and can reduce cerebral ischemia-reperfusion induced damage of neuronal cells by inhibiting calcium overload. After reviewing the relevant literature published in the past 15 years, we find that acupuncture plays a role in regulating the pathological mechanism of calcium overload after CIRI by inhibiting the opening of connexin 43 hemichannels, regulating the intracellular free calcium ion concentration, suppressing the expression of calmodulin, and blocking the function of L-type voltage-gated calcium channels, thereby inhibiting calcium overload, regulating calcium homeostasis and antagonizing neuronal damage resulted from cerebral ischemia-reperfusion, which may provide ideas for future research...
March 25, 2024: Zhen Ci Yan Jiu, Acupuncture Research
https://read.qxmd.com/read/38498092/l-type-calcium-channel-modulates-low-intensity-pulsed-ultrasound-induced-excitation-in-cultured-hippocampal-neurons
#13
JOURNAL ARTICLE
Wen-Yong Fan, Yi-Ming Chen, Yi-Fan Wang, Yu-Qi Wang, Jia-Qi Hu, Wen-Xu Tang, Yi Feng, Qian Cheng, Lei Xue
As a noninvasive technique, ultrasound stimulation is known to modulate neuronal activity both in vitro and in vivo. The latest explanation of this phenomenon is that the acoustic wave can activate the ion channels and further impact the electrophysiological properties of targeted neurons. However, the underlying mechanism of low-intensity pulsed ultrasound (LIPUS)-induced neuro-modulation effects is still unclear. Here, we characterize the excitatory effects of LIPUS on spontaneous activity and the intracellular Ca2+ homeostasis in cultured hippocampal neurons...
March 18, 2024: Neuroscience Bulletin
https://read.qxmd.com/read/38495381/genetic-alterations-in-the-neuronal-development-genes-are-associated-with-changes-of-the-tumor-immune-microenvironment-in-pancreatic-cancer
#14
JOURNAL ARTICLE
Kaiyi Mu, Juan Fu, Jessica Gai, Harshitha Ravichandran, Lei Zheng, Wei-Chih Sun
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and is highly metastatic. Our prior studies have demonstrated the critical role of axon guidance pathway genes in PDAC and the connection between neuronal development and the tumor microenvironment. A recent study newly identified 20 neuronal development genes [disks large homolog 2 ( DLG2 ), neuron-glial-related cell adhesion molecule ( NRCAM ), neurexin3 ( NRXN3 ), mitogen-activated protein kinase 10 ( MAPK10 ), platelet-derived growth factor D ( PDGFD ), protein kinase C epsilon ( PRKCE ), potassium calcium-activated channel subfamily M alpha 1 ( KCNMA1 ), polycystic kidney and hepatic disease 1 ( PKHD1 ), neural cell adhesion molecule 1 ( NCAM1 ), neuregulin-1 ( NRG1 ), zinc finger protein 667 ( ZNF667 ), cystic fibrosis transmembrane conductance regulator ( CFTR ), acyl-CoA medium-chain synthetase-3 ( ACSM3 ), complement 6 ( C6 ), protein tyrosine phosphatase receptor type M ( PTPRM ), hypoxia-inducible factor 1 alpha ( HIF1A ), adenylyl cyclase 5 ( ADCY5 ), adherens junctions-associated protein 1 ( AJAP1 ), neurobeachin ( NBEA ), sodium voltage-gated channel alpha subunit 9 ( SCN9A )] that are associated with perineural invasion and poor prognosis of PDAC...
November 2023: Annals of Pancreatic Cancer
https://read.qxmd.com/read/38492875/isradipine-an-l-type-calcium-channel-blocker-attenuates-cocaine-effects-in-mice-by-reducing-central-glutamate-release
#15
JOURNAL ARTICLE
Anna Luiza Diniz Lima, Emanuele Guimarães Silva, Pablo Leal Cardozo, Maria Carolina Machado da Silva, Suélyn Koerich, Fabíola Mara Ribeiro, Fabrício A Moreira, Luciene Bruno Vieira
Substance abuse disorder is a chronic condition for which pharmacological treatment options remain limited. L-type calcium channels (LTCC) have been implicated in drug-related plasticity and behavior. Specifically, dopaminergic neurons in the mesocorticolimbic pathway express Cav 1.2 and Cav 1.3 channels, which may regulate dopaminergic activity associated with reward behavior. Therefore, this study aimed to investigate the hypothesis that pre-administration of the LTCC blocker, isradipine can mitigate the effects of cocaine by modulating central glutamatergic transmission...
March 14, 2024: European Journal of Pharmacology
https://read.qxmd.com/read/38491746/excitotoxic-glutamate-levels-cause-the-secretion-of-resident-endoplasmic-reticulum-proteins
#16
JOURNAL ARTICLE
Amanda M Dossat, Kathleen A Trychta, Elliot J Glotfelty, Joshua J Hinkle, Lowella V Fortuno, Lana N Gore, Christopher T Richie, Brandon K Harvey
Dysregulation of synaptic glutamate levels can lead to excitotoxicity such as that observed in stroke, traumatic brain injury, and epilepsy. The role of increased intracellular calcium (Ca2+ ) in the development of excitotoxicity is well established. However, less is known regarding the impact of glutamate on endoplasmic reticulum (ER)-Ca2+ -mediated processes such as proteostasis. To investigate this, we expressed a secreted ER Ca2+ modulated protein (SERCaMP) in primary cortical neurons to monitor exodosis, a phenomenon whereby ER calcium depletion causes the secretion of ER-resident proteins that perform essential functions to the ER and the cell...
March 15, 2024: Journal of Neurochemistry
https://read.qxmd.com/read/38484627/8-shogaol-derived-from-dietary-ginger-alleviated-acute-and-inflammatory-pain-by-targeting-trpv1
#17
JOURNAL ARTICLE
Xiao-Lan Cheng, Yong-Lan Ruan, Jing-Ya Dai, Hai-Zhen Fan, Jin-Ying Ling, Jiao Chen, Wu-Guang Lu, Xue-Jiao Gao, Peng Cao
Ginger, a well-known spice plant, has been used widely in medicinal preparations for pain relief. However, little is known about its analgesic components and the underlying mechanism. Here, we ascertained, the efficacy of ginger ingredient 8-Shogaol (8S), on inflammatory pain and tolerance induced by morphine, and probed the role of TRPV1 in its analgesic action using genetic and electrophysiology approaches. Results showed that 8S effectively reduced nociceptive behaviors of mice elicited by chemical stimuli, noxious heat as well as inflammation, and antagonized morphine analgesic tolerance independent on opioid receptor function...
February 29, 2024: Phytomedicine
https://read.qxmd.com/read/38483240/experimentally-monitored-calcium-dynamics-at-synaptic-active-zones-during-neurotransmitter-release-in-neuron-muscle-cell-cultures
#18
JOURNAL ARTICLE
Xiaoping Sun, Bruce Yazejian, Arthur Peskoff, Alan D Grinnell
Ca2+ -dependent K+ (BK) channels at varicosities in Xenopus nerve-muscle cell cultures were used to quantify experimentally the instantaneous active zone [Ca2+ ]AZ resulting from different rates and durations of Ca2+ entry in the absence of extrinsic buffers and correlate this with neurotransmitter release. Ca2+ tail currents produce mean peak [Ca2+ ]AZ  ~ 30 μM; with continued influx, [Ca2+ ]AZ reaches ~45-60 μM at different rates depending on Ca2+ driving force and duration of influx...
March 14, 2024: European Journal of Neuroscience
https://read.qxmd.com/read/38482722/a-machine-learning-tool-to-identify-bistable-states-from-calcium-imaging-data
#19
JOURNAL ARTICLE
Aalok Varma, Sathvik Udupa, Mohini Sengupta, Prasanta Kumar Ghosh, Vatsala Thirumalai
Mapping neuronal activation using calcium imaging in vivo during behavioural tasks has advanced our understanding of nervous system function. In almost all of these studies, calcium imaging is used to infer spike probabilities because action potentials activate voltage-gated calcium channels and increase intracellular calcium levels. However, neurons not only fire action potentials, but also convey information via intrinsic dynamics such as by generating bistable membrane potential states. Although a number of tools for spike inference have been developed and are currently being used, no tool exists for converting calcium imaging signals to maps of cellular state in bistable neurons...
March 14, 2024: Journal of Physiology
https://read.qxmd.com/read/38480733/nanobubble-actuated-ultrasound-neuromodulation-for-selectively-shaping-behavior-in-mice
#20
JOURNAL ARTICLE
Xuandi Hou, Jianing Jing, Yizhou Jiang, Xiaohui Huang, Quanxiang Xian, Ting Lei, Jiejun Zhu, Kin Fung Wong, Xinyi Zhao, Min Su, Danni Li, Langzhou Liu, Zhihai Qiu, Lei Sun
Ultrasound is an acoustic wave which can noninvasively penetrate the skull to deep brain regions, enabling neuromodulation. However, conventional ultrasound's spatial resolution is diffraction-limited and low-precision. Here, we report acoustic nanobubble-mediated ultrasound stimulation capable of localizing ultrasound's effects to only the desired brain region in male mice. By varying the delivery site of nanobubbles, ultrasound could activate specific regions of the mouse motor cortex, evoking EMG signaling and limb movement, and could also, separately, activate one of two nearby deep brain regions to elicit distinct behaviors (freezing or rotation)...
March 13, 2024: Nature Communications
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