Advances in the knowledge and therapeutics of schizophrenia, major depression disorder, and bipolar disorder from human brain organoid research

Frontiers in Psychiatry, Год журнала: 2023, Номер 14

Опубликована: Июль 12, 2023

Tridimensional cultures of human induced pluripotent cells (iPSCs) experimentally directed to neural differentiation, termed “brain organoids” are now employed as an in vitro assay that recapitulates early developmental stages nervous tissue differentiation. Technical progress culture methodology enabled the generation regionally specialized organoids with structural and neurochemical characters distinct encephalic regions. The technical process organoid elaboration is undergoing progressively implementation, but current robustness has attracted attention psychiatric research substitute/complement animal experimentation for analyzing pathophysiology disorders. Numerous morphological, structural, molecular functional insights disorders have been uncovered by comparing brain made iPSCs obtained from control healthy subjects patients. Brain were also response conventional treatments, search new drugs, anticipate therapeutic individual patients a personalized manner. In this review, we gather data studying cerebral three most frequent serious disorders: schizophrenia, major depression disorder, bipolar disorder. Among these studies, emphasize: (i) origin pathologies takes place embryonic development; (ii) existence shared pathogenic aspects among disorders; (iii) occurrence differences between bearing same (iv) alterations can be activated or aggravated environmental signals genetic risk

Язык: Английский

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Attenuated neuronal differentiation caused by acrylamide is not related to oxidative stress in differentiated human neuroblastoma SH-SY5Y cells

Food and Chemical Toxicology, Год журнала: 2024, Номер 187, С. 114623 - 114623

Опубликована: Март 28, 2024

Acrylamide (ACR) is a known neurotoxicant and developmental neurotoxicant. As soft electrophile, ACR reacts with thiol groups in cysteine. One hypothesis of induced neurotoxicity (DNT) conjugation reduced glutathione (GSH) leading to GSH depletion, increased reactive oxygen species (ROS) production further oxidative stress cellular damage. In this regard, we have investigated the effect on neuronal differentiation, levels ROS human neuroblastoma SH-SY5Y cell model. After 9 days differentiation exposure, significantly impaired area neurites per at non-cytotoxic concentrations (0.33 μM 10 μM). Furthermore, dysregulated nine mRNA markers important for development, five them being associated cytoskeleton organization axonal guidance. At that attenuate did neither decrease level or total levels, nor production. addition, expression was assessed no significant altered regulation after exposure up 320 μM. Thus, ACR-induced DNT not due depletion production, cytotoxic concentrations, SH-SH5Y model during differentiation.

Язык: Английский

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Human pluripotent stem cells as a translational toolkit in psychedelic research in vitro

iScience, Год журнала: 2024, Номер 27(5), С. 109631 - 109631

Опубликована: Март 28, 2024

Psychedelics, recognized for their impact on perception, are resurging as promising treatments with rapid onset mood and substance use disorders. Despite increasing evidence from clinical trials, questions persist about the cellular molecular mechanisms precise correlation treatment outcomes. Murine neurons immortalized non-neural cell lines harboring overexpressed constructs have shed light neuroplastic changes mediated by serotonin 2A receptor (5-HT2AR) primary mechanism. However, limitations exist in capturing human- disease-specific traits. Here, we discuss current accomplishments prospects incorporating human pluripotent stem cells (PSCs) to complement these models. PSCs can differentiate into various brain types, mirroring endogenous expression patterns identities recreate disease phenotypes. Brain organoids derived resemble diversity patterning, while region-specific simulate circuit-level PSC-based models hold significant promise illuminate substrates of psychedelic-induced phenotypic recovery neuropsychiatric

Язык: Английский

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Transcriptomic characterization of 2D and 3D human induced pluripotent stem cell-based in vitro models as New Approach Methodologies for developmental neurotoxicity testing

Toxicology, Год журнала: 2024, Номер 510, С. 154000 - 154000

Опубликована: Ноя. 17, 2024

Язык: Английский

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Roles of Ipsc in Advancing Treatments for Neurological Disorders

Опубликована: Янв. 1, 2024

Historically, disease research in neuroscience faced limitations due to species barriers and constraints with human samples. The advent of iPSC-induced neurons represents a significant breakthrough for academic pharmaceutical research. Interdisciplinary collaborations have played pivotal role advancing iPSC technology. These yielded innovative technologies, enhanced our understanding cellular interactions expanded applications. Despite progress, challenges persist, including concerns about tumorigenicity, immune rejection, inherent heterogeneity, difficulty recapitulating sporadic diseases. Scalability issues the absence age-associated features models are notable drawbacks. This concise review examines recent advancements technology, focusing on its application addressing neurological It delves into integration industry, emphasizing roles modelling, drug discovery, screening. Looking ahead, exploration strategies, interdisciplinary collaborations, emerging technologies will continue shaping applications broader biomedical landscape. systematic analysis presentation newly developed techniques this offer roadmap overcoming obstacles, transformative impact technology development, providing new avenues understanding, treating, potentially curing

Язык: Английский

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Immortalized neuronal lines versus human induced pluripotent stem cell-derived neurons as in vitro toxicology models

Advances in neurotoxicology, Год журнала: 2024, Номер unknown, С. 47 - 81

Опубликована: Янв. 1, 2024

Язык: Английский

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Utilization of human stem cells to examine neurotoxic impacts on differentiation

Advances in neurotoxicology, Год журнала: 2024, Номер unknown, С. 137 - 172

Опубликована: Янв. 1, 2024

Язык: Английский

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S03-03: New approach methodologies (NAMs) for developmental neurotoxicity evaluation (DNT) and their use for regulatory purposes

Toxicology Letters, Год журнала: 2023, Номер 384, С. S23 - S24

Опубликована: Сен. 1, 2023

Язык: Английский

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