Understanding Lab-Grown Brain Organoids

A new scientific technique using brain organoids – mini artificial brains grown in the lab – is revealing the genetic origins of autism spectrum disorder (ASD) hidden within our brains. Called CHOOSE (which stands for CRISPR–human organoids–single-cell RNA sequencing), the technique combines elaborate genetics and quantitative bioinformatics to study mutations of genes known to be high risk for autism, and how those mutations lead to specific cell changes in the fetal brain. Because each individual cell in the tiny in vitro brain carries only one mutation (at most) for a specific high-risk gene, the effects of different mutations can be analyzed simultaneously while the cell in question divides and multiples in the growing organoid. This reveals the consequences of multiple mutations in one experiment, dramatically shortening the time required for analysis, the researchers say. https://lnkd.in/gpgkJxFG

Human cerebellar organoids with functional Purkinje cells The scientists have pioneered a novel human brain organoid model that generates all the major cell types of the cerebellum, a hindbrain region predominantly made up of two cell types necessary for movement, cognition, and emotion: granule cells and Purkinje neurons. This marks the first time that scientists have succeeded in growing Purkinje cells that possess the molecular and electrophysiological features of functional neurons in an all-human system. Other neurons within the organoids—both excitatory neurons that share information, and inhibitory neurons that inhibit the sharing of information—formed circuits and showed coordinated network activity, demonstrating that they were also functional nerve cells. In addition, organoids formed human-specific progenitor cells, which are associated with medulloblastoma, the most prevalent metastatic brain tumor in children. This makes the organoids a potentially useful model for studying and finding treatments for this pediatric cancer. #ScienceMission #sciencenewshighlights https://lnkd.in/gE-iCX3a

Aicardi Goutieres Syndrome (AGS) is among the most severe neurological conditions, and there is no cure. It is characterized by atrophy, microcephaly, and large calcifications in the brain (see image from Uggetti et al. below). Together with my Ph.D. student Gabriela Goldberg, we created a brain assembloid model containing all major cell types, such as neurons, astrocytes, oligodendrocytes, and resident microglia. Such a model revealed a misregulation in the cholesterol metabolism that induces the microglia to impair oligodendrogenesis. Interestingly, we found that the FDA-approved atorvastatin could rescue these cellular phenotypes, proving a novel therapeutic opportunity for this condition. Finally, this most advanced brain organoid model can be used to study several other neurological conditions where the interplay between the neuro-immune system is defective. You can read the article here: https://rdcu.be/dt9qU #brainorganoids #aicardigoutieres #AGS #minibrains #muotrilab #alyssonmuotri #UCSD #cholesterol #stemcells

Turning back the clock on brains aged by COVID-19. University of Queensland researchers have found a way to reverse a cellular process triggered by COVID-19 that contributes to premature ageing of the brain. Four drugs identified selectively eliminated senescent cells. Brief video included. Published: 22 November 2023 Excerpt: Dr Julio Aguado and a team from UQ’s Australian Institute for Bioengineering and Nanotechnology (AIBN) used synthetic brain organoid models, grown in a laboratory from human stem cells, to study the effect of different SARS-COV-2 variants on brain tissue. “We found COVID-19 accelerates the presence of ‘zombie’ or senescent cells, which accumulate naturally and gradually in the brain as we get older,” Dr Aguado said. “Senescent cells are known to drive tissue inflammation and degeneration, leaving patients exposed to cognitive impairments like brain fog and memory loss.” Dr Aguado said confirmation COVID-19 was a catalyst for premature ageing prompted an attempt to reset the biological brain clock. “We used the brain organoids to screen a range of therapeutics, looking for any capable of removing those senescent cells,” he said. The researchers found four drugs that selectively eliminated the cells caused by COVID-19 – navitoclax, ABT-737, fisetin and a cocktail of dasatinib plus quercetin (D+Q). Dr Aguado said the drugs rejuvenated the brain and decreased the chance of neurodegenerative symptoms in the organoids, as well as in a mouse model infected with COVID-19. “More research is needed to fully understand the mechanisms at play, but this study marks a significant step forward in knowledge of the intricate relationship between viral infections, ageing and neurological well-being,” he said. Publication: Nature Aging 13 November 2023 Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology https://lnkd.in/e-yjzZ73 https://lnkd.in/eKBu6nSj

🟦 Brain Organoids Illuminate TBI’s Link to Neurodegeneration Source: University of Southern California 🔷 Researchers have advanced our understanding of how traumatic brain injuries (#TBI) contribute to #neurodegenerative diseases using #labgrown #brain #organoids. By simulating TBI in organoids derived from human stem cells, the team observed nerve cell death and pathological changes similar to those in TBI patients, particularly in #proteins associated with #ALS and #dementia. 🔷 The discovery of the #gene #KCNJ2 as a #protective factor against TBI effects opens new avenues for treatments. This study, supported by a blend of federal and private funding, underscores the potential of #organoids in medical research and the critical role of genetics in TBI outcomes #neuroscience #genetics #neurology #tbi #also #dementia #healthtech #brainhealth #digitalhealth #healthcare #healthcare #neurotech #innovation https://lnkd.in/eCM63vSq