Could mental illness begin before they were born?

Key questions answered:

Q: When do you begin to affect genes linked to mental illness?
A: Many genes associated with neuropsychiatric and neurodegenerative diseases are active during the early stages of fetal brain development, earlier than previously believed.

Q: How did researchers discover this early genetic activity?
A: By simulating the effects of almost 3,000 genes related to the disease in fetal brain stem cells using human brain data and in vitro models, the researchers identified when and where these genes affect the processes of construction of the brain.

Q: Why is this discovery important for treatment?
A: Understanding what genes act in types of specific cells and development windows could lead to more precise custom therapies aimed at the root of mental and neurodegenerative disorders.

Summary: An innovative study has revealed that genes linked to mental and neurodegenerative disorders, such as autism, depression and Parkinson’s, begin to influence brain development during the early fetal stages. These genes are already active in neural stem cells, the parents who form the brain, long before the symptoms arise.

By combining human and mice data with laboratory cultivated cell models, researchers map how these genes behave in the stages of development and brain cell types. This opens new doors for early diagnosis, gene therapy and directed treatment of conditions that are once believed to develop later in life.

Key facts:

Early Origins: Key genes related to the disease are active in fetal neural stem cells. Rank of diseases in everything: genes linked to autism, schizophrenia, Alzheimer’s and more show early activation.

Source: Imim

The origin of some neuropsychiatric diseases, such as autism, bipolar disorder or depression, and certain neurodegenerative diseases, Alzheimer’s and Parkinson, can be found in the early stages of brain formation in the fetus.

That is, before the aforementioned, according to a study by the Research Institute of the Hospital del Mar and the University of Yale, published in Nature Communications.

The work focused “on the search for the origin of mental illnesses in the early stages of fetal development, especially in brain stem cells,” explains Dr. Gabriel Santpere, a researcher from Miguel Servet and coordinator of the neurogenomics of the research group in the Biomedical Informatics Research Program of the Research Institute Hospital, a joint group with the Pompou Fabra University.

To do this, they used a list of almost 3,000 genes linked to neuropsychiatric diseases, neurodegenerative pathologies and cortical malformations, and simulated the effect of their alteration on the cells involved in the development of the brain.

The results indicate that many of these genes are already functional during the initial phases of fetal development in stem cells, parents who build the brain, create neurons and their support structures.

Achieving this was not easy. This moment of brain development is very difficult to study. For this reason, the researchers combined multiple human brain data and mice, as well as in vitro cellular models.

As Dr. Nicola Micali, an associated researcher in the laboratory of Dr. Passko Rakic at Yale University and co-leader of research, says: “Scientists generally study the genes of mental illnesses in adults, but in this work we discover that many of these genes already act during the early stages of the formation of fetal brains Mental disorders later. “

During the study, specific regulatory networks were simulated for each type of cell involved in the development of the brain to see how the activation or deactivation of the analyzed genes linked to various brain diseases affected progenitor cells in their different stages. This allowed them to observe the importance of each gene in the appearance of alterations that cause various diseases.

The list covers from microcephaly and hydrocephalus to autism, depression, bipolar disorder, anorexia or schizophrenia, and also includes Alzheimer’s and Parkinson.

In all these pathologies, there are genes involved in the early stages of brain development when neural stem cells are functional.

“We cover a wide spectrum of diseases that the brain can have and observe how the genes involved in these conditions behave in neural stem cells,” adds Xoel Mato-Blanco, researcher at the Research Institute of the Hospital del Mar.

At the same time, he points out that the work “identifies temporary windows and types of cells where the action of these genes is more relevant, which indicates when and where it should be directed to the function of these genes.”

Having this information “is useful to understand the origin of diseases that affect cerebral cortex, that is, how genetic alterations translate into these pathologies,” says Dr. Santpere.

Understanding these mechanisms and the role of each gene in each disease can help develop directed therapies that act on them, opening opportunities for gene therapy and personalized treatments.

On this news of genetic research, mental health and neurodevelopment development

Author: Marta Calsina
Source: Imim
CONTACT: MARTA CALSINA – IMIM
Image: The image is accredited to Neuroscience News

Original research: open access.
“Early development origins of cortical disorders modeled in human neural stem cells” by Gabriel Santpere et al. Nature communications

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Early development origins of cortical disorders modeled in human neuronal stem cells

The implications of the first phases of human telencephalic development, which involve neural stem cells (NSC), in the etiology of cortical disorders are still difficult to achieve.

Here, we explore the dynamics of expression of the genes associated with the cortical and neuropsychiatric disorder in data sets generated from human NSC through transitions of the in vitro and in vivo telencephalic destiny.

We identify risk genes expressed in brain organizers and regulatory networks of sequential genes throughout corticogenesis, revealing specific critical phases of the disease when NSCs can be more vulnerable to gene dysfunction and convergent signage in multiple diseases.

In addition, we simulate the impact of the depletion of the Risk Transcription Factor (TF) on the neural cell trajectories that cross human corticogenesis and observe an effect dependent on the space-time for each disturbance.

Finally, the transcriptomic of individual cells of the NSC in vitro derived from patients affected by autism reveals the alteration of the recurrent expression of TFS orchestrating the brain pattern and the commitment of lineage of NSC.

This work opens perspectives to explore human cerebral dysfunction in the early stages of development.