Опубликована: Янв. 1, 2024
Язык: Английский
Development, Год журнала: 2024, Номер 151(10)
Опубликована: Май 15, 2024
ABSTRACT In utero infection and maternal inflammation can adversely impact fetal brain development. Maternal systemic illness, even in the absence of direct infection, is associated with an increased risk neuropsychiatric disorders affected offspring. The cell types mediating response to are largely unknown, hindering development novel treatment strategies. Here, we show that microglia, resident phagocytes brain, highly express receptors for relevant pathogens cytokines throughout embryonic Using a rodent immune activation (MIA) model which polyinosinic:polycytidylic acid injected into pregnant mice, demonstrate long-lasting transcriptional changes microglia persist postnatal life. We find MIA induces widespread gene expression neuronal non-neuronal cells; importantly, these responses abolished by selective genetic deletion indicating required other cortical MIA. These findings play crucial durable role inflammation, should be explored as potential therapeutic targets.
Язык: Английский
Процитировано
12
Journal of Neuroimmune Pharmacology, Год журнала: 2024, Номер 19(1)
Опубликована: Март 27, 2024
Abstract Autism spectrum disorder (ASD) is a neurological associated with brain inflammation. The underlying mechanisms could be attributed to the activation of PI3K signaling in inflamed ASD. Multiple studies highlight role GRPR regulating ASD like abnormal behavior and enhancing signaling. However, molecular mechanism by which regulates neurons individuals still unclear. In this study, we utilized maternal immune model investigate effects on mice. We used HT22 cells without examine impact GRP-GRPR PI3K-AKT pathway IL-6 treatment. analyzed dataset hippocampus samples from mice identify hub genes. Our results demonstrated increased expression IL-6, GRPR, Additionally, observed PI3K-AKT/mTOR after treatment, but decreased knockdown. NetworkAnalyst identified GSK-3β as most crucial gene Furthermore, found that upregulated upregulating GRP-GRPR. findings suggest can enhance PI3K-AKT/mTOR-GSK-3β hippocampal GRPR. Graphical
Язык: Английский
Процитировано
9
Oxford Open Neuroscience, Год журнала: 2024, Номер 3
Опубликована: Янв. 1, 2024
Autism spectrum disorder (ASD) affects 1 in 36 people and is more often diagnosed males than females. Core features of ASD are impaired social interactions, repetitive behaviors deficits verbal communication. a highly heterogeneous heritable disorder, yet its underlying genetic causes account only for up to 80% the cases. Hence, subset cases could be influenced by environmental risk factors. Maternal immune activation (MIA) response inflammation during pregnancy, which can lead increased inflammatory signals fetus. Inflammatory cross placenta blood brain barriers affecting fetal development. Epidemiological animal studies suggest that MIA contribute etiology. However, human mechanistic have been hindered lack experimental systems replicate impact Therefore, mechanisms altered pre-natal development, underlie pathogenesis largely understudied. The advent cellular models with induced pluripotent stem cell (iPSC) organoid technology closing this gap knowledge providing both access molecular manipulations culturing capability tissue would otherwise inaccessible. We present an overview multiple levels evidence from clinical, epidemiological, provide potential link between higher inflammation. More importantly, we discuss how cell-derived may constitute ideal system mechanistically interrogate effect early stages
Язык: Английский
Процитировано
7
Brain Behavior and Immunity, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 1, 2024
Язык: Английский
Процитировано
5
Environment & Health, Год журнала: 2024, Номер 2(6), С. 332 - 349
Опубликована: Фев. 28, 2024
In recent years, rapid industrial development has resulted in the production and exposure of a substantial number compounds to human body. This created an urgent need environmental toxicology for models that are efficient, accurate, cost-effective evaluating health impacts these on humans. Over past seven decades, various cancer cell lines immortalized have made significant contributions advancement research organ toxicity. Pluripotent stem technology, especially toxicological derived from pluripotent cells, presents modern toxicologists with high-throughput, species-relevant, predictive options. this comprehensive review, we assess characteristics representative toxicology, as well introduce two distinct types their innovative models. We explore applications prospects field while also addressing readiness vitro confront emerging challenges future.
Язык: Английский
Процитировано
4
Droplet, Год журнала: 2025, Номер unknown
Опубликована: Янв. 9, 2025
Abstract Research on cells and organ‐like tissues is critical in the fields of molecular biology, genetic analysis, proteomics tissue engineering, others. In recent years, advancements precise cell manipulation technologies have made positioning batch processing feasible. Various methods are used for recognition, positioning, manipulation, assembly, often introducing external such as electric, magnetic, acoustic, or optical into liquid environment to interact with cells, applying forces induce movement rearrangement. Alternatively, three‐dimensional (3D) bioprinting technology employed assembly. This review will comprehensively assess status, principles, advantages, disadvantages, prospects these technologies, covering single‐cell multicellular biological 3D printing techniques.
Язык: Английский
Процитировано
0
Trends in Cell Biology, Год журнала: 2025, Номер unknown
Опубликована: Янв. 1, 2025
Brain organoids are important 3D models for studying human brain development, disease, and evolution. To overcome some of the existing limitations that affect organoid quality, reproducibility, characteristics, in vivo resemblance, current efforts directed to improve their physiological relevance by exploring different, yet interconnected, routes. In this review, these approaches latest developments discussed, including stem cell optimization, refining morphogen administration strategies, altering extracellular matrix (ECM) niche, manipulating tissue architecture mimic morphogenesis. Additionally, strategies increase diversity enhance maturation, such as establishing co-cultures, assembloids, xenotransplantation, reviewed. We explore how various factors can be tuned intermingled speculate on future avenues towards even more physiologically-advanced organoids.
Язык: Английский
Процитировано
0
Biological Psychiatry, Год журнала: 2025, Номер unknown
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0
Journal of Neuroimmune Pharmacology, Год журнала: 2025, Номер 20(1)
Опубликована: Фев. 22, 2025
Most current information about neurological disorders and diseases is derived from direct patient animal studies. However, studies in many cases do not allow replication of the early stages disease and, therefore, offer limited opportunities to understand progression. On other hand, although use models allows us study mechanisms disease, they present significant limitations developing drugs for humans. Recently, 3D-cultured vitro human pluripotent stem cells have surfaced as a promising system. They potential connect findings with those models. In this comprehensive review, we discuss their application modeling neurodevelopmental conditions such Down Syndrome or Autism, neurodegenerative Alzheimer's Parkinson's, viral like Zika virus HIV. Furthermore, will different used prenatal exposure abuse, well challenges that must be met transform landscape research on brain disorders.
Язык: Английский
Процитировано
0
Current Opinion in Pediatrics, Год журнала: 2025, Номер 37(2), С. 182 - 190
Опубликована: Фев. 12, 2025
Applying discoveries from basic research to patients in the neonatal intensive care unit (NICU) is challenging given difficulty of modeling this population animal models, lack translational relevance models humans, and scarcity primary human tissue. Human cell-derived cerebral organoid are an appealing way address some these gaps. In review, we will touch on previous work model conditions organoids, limitations approach, recent strategies that have attempted limitations. While neurodevelopmental disorders has been application organoids since their initial description, studies dramatically expanded types brain regions disease available. Additionally, increase complexity by including immune vascular cells, as well heterogeneity with mixed donor provide new opportunities pathologies. Organoids attractive study pathologies relevant ICU. New technologies broaden applicability usefulness a drug screening platform.
Язык: Английский
Процитировано
0