In various spheres of medicine, they have been used brain organoids mutants to better understand the dynamics that characterize certain pathologies. Scientists from” Institute of Science and Technology Austria (ISTA) have decided to exploit this approach to better study the characteristics of the autism spectrum disorder.
The result of the Research was published in the scientific journal Cell Reports.
Having already possessed all types of cells in organoids, scientists have identified that mutant brain organoids have begun to produce a specific type of neurons, the so-called inhibitory neurons. The so-called excitatory neurons, instead, they were produced later.
Furthermore, the mutant brain organoids produced much more proliferating cells which subsequently produced more of this type of neurons.. Overall, the scientists’ conclusion was that this leads to them being significantly larger than organoids without them CHD8 mutations related to the patient’s macrocephaly.
Like the previous studies of the Novarino group, their recent study shows how important time is when studying autism: “Observing different moments gives us the information that what we see in the end may not be the complete picture of how a patient’s brain has developed, much more may have happened before “Novarino said.
“We still have a limited understanding of how different trajectories affect brain functions. To help patients with a CHD8 mutation someday, the basics of brain development need to be better understood. By reproducing the genetic and clinical characteristics of patients with ASD in brain organoids, the Novarino group was able to make an important contribution“, Continued the expert.
Chromodomain-helicase-DNA binding protein 8 (CHD8) has been identified as one of the genes with the strongest association with autism. The CHD8 protein is a transcriptional regulator expressed in nearly all cell types and has been implicated in multiple cellular processes, including cell cycle, cell adhesion, neuronal development, myelination, and synaptogenesis.
Considering the central role of CHD8 in autism genetics, a deeper understanding of the physiological functions of CHD8 is important for understanding the development of the autism phenotype and potential therapeutic targets. Several CHD8 mutant mouse models have been developed to determine autism-like phenotypes and to fully understand their mechanisms.
Chromodomain-helicase-DNA binding protein 8 (CHD8) was first linked to ASD about a decade ago when de novo mutations were first identified in two children with ASD. Since then, several studies have shown that various disruptive mutations in both CHD8 isoforms are correlated with an increased risk of ASD and could characterize an ASD subtype.
Most of the known CHD8 mutations lead to loss of protein function. In individuals with ASD, CHD8 mutations were found to be more abundant in males. In a cohort of approximately 6000 individuals with autism, 0.2% had de novo mutations specifically in CHD8, further demonstrating that CHD8 dysfunction is an important factor in ASD pathology.
Being able to evaluate CHD8 mutations through mutant brain organoids would bring a big breakthrough in understanding the change and consequently the autism spectrum disorder, given the mutation in question has the strongest association with autism. Once the dynamics are revealed, new therapeutic frontiers would open up in the treatment of ASD.
Brain organoids do not have a conscience and do not think, but they have proved very useful in the study of neurodegenerative diseases. Generally, they are developed in the laboratory from stem cells donated by patients, so that they can identify the early stages of various pathologies and be able to give life to new therapies that are more promising than the current ones.
In Cambridge, a research team reproduced a brain organoid in 3D from stem cells from a patient with amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia. Scientists sThey managed to keep these mini-brains alive in the lab for over a year, a result never achieved before, thanks to which it was possible to detect structural and functional changes in the cerebral cortex, which could take place as early as birth. The results were published on Nature Neurosciences.
The same results could be replicated on the cast of a disorder still to be discovered such as that of the autism spectrum.
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