Publications by authors named "F Gage"

As the field of neural organoids and assembloids rapidly expands, there is an emergent need for guidance and advice on designing, conducting and reporting experiments to increase the reproducibility and utility of these models. Here, our consortium- representing specialized laboratories from around the world- presents a framework for the experimental process that ranges from ensuring the quality and integrity of human pluripotent stem cells to characterizing and manipulating neural cells in vitro, and from transplantation techniques to considerations for modeling human development, evolution, and disease. As with all scientific endeavors, we advocate for rigorous experimental designs tailored to explicit scientific questions, and transparent methodologies and data sharing, to provide useful knowledge for both current research practices and for developing regulatory standards.

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In the adult dentate gyrus of the hippocampus there are neuronal stem cells that give rise to immature neurons and subsequently to mature functional granule neurons. The rate of proliferation, differentiation, and survival is regulated intrinsically and extrinsically. For example, Wnt, BMP, TLX, and BDNF all regulate adult neurogenesis intrinsically, while exercise, environmental enrichment, stress, and epilepsy are some of the extrinsic factors that regulate adult neurogenesis.

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  • * Knockdown of miR-124 leads to significant alterations in the oxidative phosphorylation pathway, resulting in mitochondrial dysfunctions like reduced membrane potential and impaired cellular respiration.
  • * The study suggests that specific proteins, like GSTK1, may serve as novel metabolic regulators, potentially linking metabolic dysregulation in neurons to various human brain disorders.
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  • Impaired glucose metabolism in the brain is a key feature of Alzheimer's disease, with recent studies showing that glial cell metabolism is disrupted.
  • Inhibition of the enzyme IDO1, which converts tryptophan into kynurenine, can improve memory function in mouse models of Alzheimer's by restoring how astrocytes (a type of brain cell) metabolize.
  • IDO1 inhibition not only enhances glucose metabolism in the brain but also boosts the production of lactate, which is beneficial for neurons, suggesting potential for IDO1 inhibitors, originally designed for cancer, to be used in Alzheimer's treatment.
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  • Age-related neurodegenerative diseases, such as Alzheimer's, currently have no cure and limited treatment options, making them particularly difficult to manage.
  • Human stem cell-derived brain organoids offer a promising method to study Alzheimer's disease by mimicking human brain structure and pathology, which may help reveal how the disease affects neural cells and cognitive function.
  • This review examines the strategies for using brain organoids in Alzheimer's research while also discussing the challenges faced when studying age-related brain disorders with these models.
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