Oxytocin accelerates tight junction formation and impairs cellular migration in 3D spheroids: evidence from Gapmer-induced exon skipping DOI Creative Commons
Benjamin Jurek,

Lucia Denk,

Nicole Schäfer

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: Oct. 3, 2022

Oxytocin (OXT) is a neuropeptide that has been associated with neurological diseases like autism, strong regulating activity on anxiety and stress-related behavior, physiological effects during pregnancy parenting, various cellular in neoplastic tissue. In this study, we aimed to unravel the underlying mechanism OXT employs regulate cell-cell contacts, spheroid formation, migration 3D culture model of human MLS-402 cells. We have generated labeled receptor (OXTR) overexpressing cell line cultivated spheroids were treated OXTR agonists OXT, Atosiban, Thr4-Gly7-oxytocin (TGOT); or without pre-treatment antisense oligos (Gapmers) induce exon skipping gene. This leads exclusion 4 therefore lost its intracellular G-protein-binding domain. Sensitive digital PCR (dPCR) provided us means differentiate between wild type truncated our model. truncation differentially activated signaling cascades related attachment proliferation Akt, ERK1/2-RSK1/2, HSP27, STAT1/5, CREB, as assessed by Kinase Profiler Assay. Digital transmission electron microscopy revealed increased tight junction formation well-organized protrusions into an enlarged extracellular space after treatment, resulting survival. summary, decreases but increases contacts improves nutrient supply. These data reveal novel effect might implications for degenerating CNS tumor tissues.

Language: Английский

Advances in human oxytocin measurement: challenges and proposed solutions DOI Creative Commons
Benjamin A. Tabak, Gareth Leng,

Angela Szeto

et al.

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 28(1), P. 127 - 140

Published: Aug. 23, 2022

Oxytocin, a neuropeptide known for its role in reproduction and socioemotional processes, may hold promise as therapeutic agent treating social impairments patient populations. However, research has yet to uncover precisely how manipulate this system clinical benefit. Moreover, inconsistent use of standardized validated oxytocin measurement methodologies-including the design study hormone secretion biochemical assays-present unresolved challenges. Human studies measuring peripheral (i.e., plasma, saliva, or urine) central cerebrospinal fluid) concentrations have involved very diverse methods, including different assay techniques, further compounding problem. In present review, we describe scientific value human endogenous concentrations, common issues analysis that researchers face when doing so, our recommendations improving using valid reliable methodologies.

Language: Английский

Citations

98
Detection, processing and reinforcement of social cues: regulation by the oxytocin system DOI
Rohit Menon, Inga D. Neumann

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 24(12), P. 761 - 777

Published: Oct. 27, 2023

Language: Английский

Citations

44
Oxytocin alleviates cognitive and memory impairments by decreasing hippocampal microglial activation and synaptic defects via OXTR/ERK/STAT3 pathway in a mouse model of sepsis-associated encephalopathy DOI
Junliang Jiang, Yue Zou, Chuantong Xie

et al.

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 114, P. 195 - 213

Published: Aug. 28, 2023

Language: Английский

Citations

27
AI-based identification of therapeutic agents targeting GPCRs: introducing ligand type classifiers and systems biology DOI Creative Commons
Jonas Goßen, Rui P. Ribeiro, Dirk Bier

et al.

Chemical Science, Journal Year: 2023, Volume and Issue: 14(32), P. 8651 - 8661

Published: Jan. 1, 2023

Identifying ligands targeting G protein coupled receptors (GPCRs) with novel chemotypes other than the physiological is a challenge for in silico screening campaigns. Here we present an approach that identifies chemotype by combining structural data random forest agonist/antagonist classifier and signal-transduction kinetic model. As test case, apply this to identify antagonists of human adenosine transmembrane receptor type 2A, attractive target against Parkinson's disease cancer. The identified were tested here radio ligand binding assay. Among those, found promising whose differs significantly from all so-far reported antagonists, affinity 310 ± 23.4 nM. Thus, our protocol emerges as powerful candidates while preserving antagonistic potential nanomolar range.

Language: Английский

Citations

11
Decoding the genetic landscape of autism: A comprehensive review DOI Open Access
Mohammed Al‐Beltagi,

Nermin Kamal Saeed,

Adel Salah Bediwy

et al.

World Journal of Clinical Pediatrics, Journal Year: 2024, Volume and Issue: 13(3)

Published: Aug. 29, 2024

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by heterogeneous symptoms and genetic underpinnings. Recent advancements in epigenetic research have provided insights into the intricate mechanisms contributing to ASD, influencing both diagnosis therapeutic strategies.

Language: Английский

Citations

3
Functional significance of some common oxytocin receptor SNPs involved in complex human traits DOI Creative Commons
Suk Ling, Michael T. Bowen, Mark R. Dadds

et al.

BMC Molecular and Cell Biology, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 6, 2025

Abstract Background Oxytocin function is associated with a range of human traits and often indexed by common polymorphisms the receptor gene OXTR. Little known however about functional significance these polymorphisms. Objectives To examine effects OXTR on transcription expression in neural cells. Method The impact four SNPs (rs1042778, rs4686302, rs2254298 rs237887) were tested neuroblastoma cell line, SH-SY5Y, commonly used line for neurological disease. chosen as having robust evidence associations complex after consideration linkage patterns across Results level GG genotype rs1042778 was significantly lower than TT genotypes. None other related to transcription. Conclusions showing are not reliably changes Increasing cooperation between behavioral biological scientists needed bridge gap trait studies improve our understanding oxytocin important mammalian neuroendocrine processes.

Language: Английский

Citations

0
Predicting oxytocin binding dynamics in receptor genetic variants through computational modeling DOI Creative Commons

Preeti Dubey,

Yingye Fang, K. Lionel Tukei

et al.

npj Women s Health, Journal Year: 2025, Volume and Issue: 3(1)

Published: Feb. 8, 2025

Language: Английский

Citations

0
Dual-signal enrichment enhanced entropy-driven circuits integrated ligases for highly sensitive genotyping detection DOI

Qianglong Tan,

Yunshan Zhang, Fang Yang

et al.

Sensors and Actuators B Chemical, Journal Year: 2025, Volume and Issue: unknown, P. 137694 - 137694

Published: March 1, 2025

Language: Английский

Citations

0
Structural Systems Biology Toolkit (SSBtoolkit): From Molecular Structure to Subcellular Signaling Pathways DOI
Rui P. Ribeiro, Jonas Goßen, Giulia Rossetti

et al.

Journal of Chemical Information and Modeling, Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Here, we introduce the Structural Systems Biology (SSB) toolkit, a Python library that integrates structural macromolecular data with systems biology simulations to model signal-transduction pathways of G-protein-coupled receptors (GPCRs). Our framework streamlines simulation and analysis mathematical models GPCRs cellular pathways, facilitating exploration kinetics induced by ligand-GPCR interactions: dose-response ligand can be modeled, along corresponding change in concentration other signaling molecular species over time, like for instance [Ca2+] or [cAMP]. SSB toolkit brings light possibility easily investigating subcellular effects binding on receptor activation, even presence genetic mutations, thereby enhancing our understanding intricate relationship between ligand-target interactions at level higher-level (patho)physiological response mechanisms.

Language: Английский

Citations

0
Faded neural projection from the posterior bed nucleus of the stria terminalis to the lateral habenula contributes to social signaling deficit in male BTBR mice as a mouse model of autism DOI Creative Commons
Yuki Higuchi,

Shun-ichi Tachigori,

Hiroyuki Arakawa

et al.

Psychoneuroendocrinology, Journal Year: 2022, Volume and Issue: 149, P. 106004 - 106004

Published: Dec. 16, 2022

BTBR T+ Itpr3tf/J (BTBR) mice display several behavioral characteristics, including social deficits resembling the core symptoms of human autism. Atypical behaviors include sequential processes assembled cognitive-behavior components, such as recognition, investigatory assessment, and signaling response. This study aimed to elucidate neural circuits responsible for regulation response, shown by scent marking behavior in male mice. We first assessed recognition patterns compared those C57BL/6 J (B6) Next, we examined their scent-marking innate responses adjusted a confronted feature stimuli situations, along with expression c-Fos marker neuronal activity selected brain areas involved behavior. The function targeted area was confirmed chemogenetic manipulation. also peptides, oxytocin vasopressin neurons major regions that are associated Our data indicate less responsive presentation responses, which is paralleled blunted responsivity morphological changes areas, posterior bed nucleus stria terminalis (pBnST) lateral habenula (LHb) Further investigation LHb revealed inhibition activation can induce change both B6 elucidation downstream controlling indicates intact altered characteristics paraventricular hypothalamus vasopressin-positive axonal projections pBnST appear underlie dysfunction (300/300 words).

Language: Английский

Citations

11