A Comprehensive Review on Utilizing Human Brain Organoids to Study Neuroinflammation in Neurological Disorders

Journal of Neuroimmune Pharmacology, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 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.

Language: Английский

---

Advancements in 3D models for studying human iPSC-microglia: Insights into neurodevelopment and neurological disorders

hLife, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

---

Dopamine-driven increase in IL-1β in myeloid cells is mediated by differential dopamine receptor expression and exacerbated by HIV

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: March 23, 2025

The catecholamine neurotransmitter dopamine is classically known for regulation of central nervous system (CNS) functions such as reward, movement, and cognition. Increasing evidence also indicates that regulates critical in peripheral organs an important immunoregulatory factor. We have previously shown increases NF-κB activity, inflammasome activation, the production inflammatory cytokines IL-1β human macrophages. As myeloid lineage cells are to initiation resolution acute responses, dopamine-mediated dysregulation these could both impair innate immune response exacerbate chronic inflammation. However, exact pathways by which drives inflammation not well defined, studies rodent systems indicate can impact mediators through D1-like receptors (DRD1, DRD5) D2-like (DRD2, DRD3, DRD4). Therefore, we hypothesized regulated ratio different activated. Our data primary monocyte-derived macrophages (hMDM) DRD1 expression necessary IL-1β, changes DRD2 other alter magnitude increase IL-1β. Mature hMDM a high receptor ratio, relative monocytes blood mononuclear (PBMCs). further confirm microglia cell lines promotes dopamine-induced gene protein using pharmacological inhibition or overexpression receptors. RNA-sequencing dopamine-treated shows genes encoding signaling pathways, neurotransmission increased with treatment. Finally, HIV example disease substantively worsened comorbid substance use disorders (SUDs) dopaminergic signaling, show effects on activation presence microglia. These suggest addictive substances dopamine-modulating therapeutics dysregulate neuroimmunological conditions like HIV. Thus, detailed understanding inflammation, particular regulating will be effectively tailor medication regimens.

Language: Английский

---

Dopamine-driven Increase in IL-1β in Myeloid Cells is Mediated by Differential Dopamine Receptor Expression and Exacerbated by HIV

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 10, 2024

The catecholamine neurotransmitter dopamine is classically known for regulation of central nervous system (CNS) functions such as reward, movement, and cognition. Increasing evidence also indicates that regulates critical in peripheral organs an important immunoregulatory factor. We have previously shown increases NF-κB activity, inflammasome activation, the production inflammatory cytokines IL-1β human macrophages. As myeloid lineage cells are to initiation resolution acute responses, dopamine-mediated dysregulation these could both impair innate immune response exacerbate chronic inflammation. However, exact pathways by which drives inflammation not well defined, studies rodent systems indicate can impact mediators through D1-like receptors (DRD1, DRD5) D2-like (DRD2, DRD3, DRD4). Therefore, we hypothesized regulated ratio different activated. Our data primary monocyte-derived macrophages (hMDM) DRD1 expression necessary IL-1β, changes DRD2 other alter magnitude increase IL-1β. Mature hMDM a high receptor ratio, relative monocytes blood mononuclear (PBMCs). further confirm microglia cell lines promotes dopamine-induced gene protein using pharmacological inhibition or overexpression receptors. RNA-sequencing dopamine-treated shows genes encoding signaling pathways, neurotransmission increased with treatment. Finally, HIV example disease substantively worsened comorbid substance use disorders (SUDs) dopaminergic signaling, show effects on activation presence microglia. These suggest addictive substances dopamine-modulating therapeutics dysregulate neuroimmunological conditions like HIV. Thus, detailed understanding inflammation, particular regulating will be effectively tailor medication regimens.

Language: Английский

---

Recent advances in brain organoids: a comprehensive review of the last eight years

New discovery., Journal Year: 2024, Volume and Issue: unknown, P. 1 - 14

Published: Oct. 31, 2024

Organoids are three-dimensional cellular structures grown in vitro that can self-organize and differentiate into cell types with organ-specific functions, closely mimicking the biological properties of tissues organs vivo. Brain organoids, which resembling brain function, serve as valuable models for medical research, including disease microenvironment simulation, mechanism exploration, drug evaluation. In this review, we analyzed 808 articles retrieved from PubMed, CNKI, Wanfang databases using keyword "brain organoids," 180 were included. We summarized research progress organoids over past eight years by categorizing refining findings. Our analysis shows have achieved significant success simulating development vitro, leading to establishment refinement 3D organoid research. been widely applied explore disease-related mechanisms, yielding promising results opening avenues further on human brain. summarize three areas: culture methods, exploration.

Language: Английский

---

Polygenic risk for alcohol use disorder affects cellular responses to ethanol exposure in a human microglial cell model

Science Advances, Journal Year: 2024, Volume and Issue: 10(45)

Published: Nov. 8, 2024

Polygenic risk scores (PRSs) assess genetic susceptibility to alcohol use disorder (AUD), yet their molecular implications remain underexplored. Neuroimmune interactions, particularly in microglia, are recognized as notable contributors AUD pathophysiology. We investigated the interplay between PRS and ethanol human microglia derived from iPSCs individuals with high-PRS (diagnosed AUD) or low-PRS (unaffected). Ethanol exposure induced elevated CD68 expression morphological changes differential responses microglial cells. Transcriptomic analysis revealed differences MHCII complex phagocytosis-related genes following exposure; cells displayed enhanced phagocytosis increased

Language: Английский

---