Answered: Essential Questions
Q: When does the mind begin to be affected by genes linked to emotional condition?
A: Many genes associated with neuropsychiatric and neurodegenerative diseases are active during the earliest stages of fetal brain development—far earlier than previously believed.
Q: How did scientists find this first biological action?
A: By simulating the effects of nearly 3,000 disease-related genes in fetal brain stem cells using human and mouse brain data and in vitro models, researchers identified when and where these genes impact brain-building processes.
Q: Why is this finding crucial for care?
A: Understanding which genes act in specific cell types and developmental windows could lead to more precise, personalized therapies targeting the root of mental and neurodegenerative disorders.
Summary: A pioneering study has discovered that the earliest maternal stages of gene expression are first impacted by genes linked to emotional and neurological disorders like autism, depression, and Parkinson’s. Before signs appear, these genes are already present in neural stem cells, the brain’s forebears, long before they become apparent.
Researchers compared the behavior of these genes across various developmental levels and brain cell types by combining data from humans and mice with lab-grown body models. This opens up the possibility of treating problems that were previously thought to build later in life, such as early diagnosis and gene therapy.
Important Information
- First Origins: In maternal neural stem cells, important disease-related genes are effective.
- Broad Spectrum of Diseases: Genes associated with autism, psychosis, Alzheimer’s, and other conditions display early activation.
- Results may serve as a guide for targeted therapies and first interventions.
IMIM Resource
Some neurological conditions, such as dementia, bipolar illness, or sadness, and some degenerative diseases, Alzheimer’s and Parkinson’s, can be found in , very early stages of mental development in the infant.
That is, earlier than previously thought, according to a research conducted by Yale University and the Hospital del Mar Research Institute, which was published in Nature Communications.
According to Dr. Gabriel Santpere, Miguel Servet scholar and representative of the Neurogenomics Research Group at the Biomedical Informatics Research Program of the Hospital del Mar Research Institute, a combined class with Pompeu Fabra University, the analysis focuses on “looking for the source of psychological ailments in the earliest stages of fetal development, especially in the brain stem cells.”
In order to accomplish this, they simulated the effects of their alteration on the cells involved in brain development by using a list of , nearly 3, 000 genes linked to neuropsychiatric diseases, neurodegenerative pathologies, and cortical malformations.
The results demonstrate that many of these genes are already present during the fetal stages of development, as well as in the development of stem cells, the brain’s progenitors, and the creation of neurons and their supporting structures.
This was challenging. This stage of brain development is challenging to comprehend. For this reason, the researchers combined multiple data sets from in vitro cellular models, human brains, and mice brains.
According to Dr. Nicola Micali, associate researcher at Dr. Pasko Rakic’s lab at Yale University and co-leader of the study, “scientists typically study the genes that cause mental illnesses in adults, but we discovered that many of these genes already act during the early stages of fetal brain development and can later lead to the development of mental disorders.”
In order to understand how the activation or deactivation of the analyzed genes linked to various brain diseases affected progenitor cells at various stages during the study, specific regulatory networks for each cell type involved in brain development were simulated. In this way, they were able to determine the significance of each gene in how many alterations cause various illnesses.
The list includes Alzheimer’s and Parkinson’s, as well as autism, depression, bipolar disorder, anorexia, and schizophrenia.
All of these pathologies contain genes that are present in neural stem cells during the initial stages of brain development.
We examine how the genes involved in these conditions behave in neural stem cells and cover a wide range of brain conditions, according to Xoel Mato-Blanco, a researcher at the Hospital del Mar Research Institute.
He also points out that the research “identifies temporal windows and cell types where the action of these genes is most important, indicating when and where you should target the function of these genes.”
According to Dr. Santpere, having this information “is useful to understand the origin of diseases that affect the cerebral cortex, and how genetic alterations can be used to explain these pathologies.”
Understanding these mechanisms and the function of each gene in each disease can help develop targeted therapies that act on them, opening up opportunities for gene , therapy, and personalized treatments.
About this news from research in neurodevelopment, mental health, and genetics
Author: Marta Calsina
Source: IMIM
Contact: Marta Calsina – IMIM
Image: The image is credited to Neuroscience News
Open access to original research.
Gabriel Santpere and colleagues ‘” Early neural stem cell models of cortical disorders in humans.” Nature Communications
Abtract
Early neural stem cell models of cortical disorders in humans
The early stages of human telencephalic development, which involve neural stem cells ( NSCs ), remain elusive in terms of the etiology of cortical disorders.
In vitro and in vivo studies of the expression dynamics of cortical and neuropsychiatric disorder-associated genes from datasets created from human NSCs, we investigate these findings.
We find risk genes that are expressed in brain organizers and sequential gene regulatory networks throughout corticogenesis, revealing critical disease-specific times when NSCs may be more susceptible to gene dysfunction and convergent signaling across multiple diseases.
Further, we perform a spatiotemporal-dependent analysis of the effects of risk transcription factor ( TF ) depletions on neural cell trajectories traversing human corticogenesis and map out the effects of each perturbation.
Finally, single-cell transcriptomics of patient-derived autism-affected NSCs in vitro reveal recurrent expression alteration of TFs responsible for NSC lineage commitment and brain patterning.
This research opens up new avenues to investigate how human brain dysfunction develops in the first few years.
