A recent investigation has uncovered that childhood abuse or neglect can initiate an excessive process of synapse removal in the brain facilitated by astrocytes due to the presence of stress hormones. This phenomenon ultimately leads to the development of mental illnesses. Researchers employed an FDA-approved medication and determined that stress hormones, known as glucocorticoids, contribute to abnormal levels of astrocyte-mediated synapse removal, thus playing a role in the onset of mental health conditions.
Childhood maltreatment can initiate considerable stress, which subsequently reshapes neural pathways and functions during brain maturation. These alterations predispose individuals to conditions like depression and schizophrenia. Nonetheless, the precise mechanism and methods to control this process remained elusive.
On August 1, a group of scientists led by Professor Won-Suk Chung from the Department of Biological Sciences at KAIST announced their findings regarding excessive synapse removal through astrocyte involvement as the root cause of mental disorders triggered by childhood abuse trauma. This groundbreaking research was published in Immunity, a prominent international journal in the field of immunology.
The researchers revealed that the excessive removal of excitatory synapses in the brain, facilitated by astrocytes in response to stress hormones, is a fundamental cause of mental disorders linked to childhood neglect and abuse. Previous clinical data had suggested that high stress levels could lead to various mental disorders, but the precise mechanism was unknown. Consequently, the outcomes of this study are expected to have broad applications in preventing and treating such conditions.
The team examined an FDA-approved drug to elucidate the mechanism governing astrocytes’ phagocytic role – their ability to capture and eliminate external substances. As a result, the researchers found that synthetic glucocorticoids, or stress hormones, significantly heightened astrocyte-mediated phagocytosis to an abnormal degree.
Glucocorticoids play vital roles in essential life processes like carbohydrate metabolism and anti-inflammatory responses. However, they are also released in response to external stressors, enabling the body to adapt. Yet, prolonged and excessive exposure to glucocorticoids due to chronic stress can result in various mental disorders, including depression, cognitive impairments, and anxiety.
To comprehend how childhood stress affects astrocyte functions, the researchers used mouse models subjected to early social deprivation. They discovered that stress hormones bind to astrocytes’ glucocorticoid receptors (GRs), leading to a substantial increase in the expression of Mer tyrosine kinase (MERK), a crucial player in astrocyte phagocytosis.
Notably, astrocytes selectively targeted excitatory synapses of specific neurons among the various neurons in the cerebral cortex. This process contributed to the formation of abnormal neural networks, which could subsequently lead to complex behavioral abnormalities such as social deficits and adult-onset depression.
The study also observed that microglia, which are essential for cerebral immunity, did not participate in synapse removal in the mouse models subjected to early social deprivation. This confirmed that the response to childhood stress hormones primarily involves astrocytes.
To confirm the relevance of their findings to humans, the research team utilized brain organoids grown from human-induced pluripotent stem cells to observe how human brain cells respond to stress hormones. The team noted that stress hormones induced astrocyte glucocorticoid receptors and triggered phagocytic activation in the human brain organoids, ultimately leading to excessive elimination of excitatory synapses. The consistency between the responses in mice and human brain organoids suggests that this newly discovered mechanism applies to mental disorders in humans as well.
Professor Won-Suk Chung remarked, “Up until now, we lacked a precise understanding of how childhood stress could lead to brain disorders. This research is the first to demonstrate that excessive astrocyte phagocytosis might be a significant underlying cause of such conditions.” He further added, “In the future, regulating astrocyte immune responses could serve as a fundamental target for comprehending and treating brain disorders.”
Source: Adapted from “New Research Unveils How Childhood Abuse Triggers Mental Diseases” (original text)
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Frequently Asked Questions (FAQs) about Childhood Trauma
What does the research reveal about childhood trauma and mental disorders?
The research uncovers that childhood abuse or neglect can lead to excessive removal of brain synapses by astrocytes due to stress hormones. This process contributes to mental disorders like depression and schizophrenia.
How do stress hormones play a role in this process?
Stress hormones, known as glucocorticoids, enhance astrocyte-mediated synapse removal to abnormal levels, ultimately contributing to the development of mental illnesses.
What are astrocytes and their role in this context?
Astrocytes are a type of brain cell that play a crucial role in supporting and regulating neuronal function. In response to stress hormones, astrocytes can remove synapses, affecting neural pathways and potentially leading to mental disorders.
How does childhood trauma impact brain development?
Childhood trauma, such as abuse or neglect, induces significant stress that can alter neural pathways during brain development. These changes increase the risk of individuals developing conditions like depression and schizophrenia later in life.
What are the implications of these findings for mental health treatment?
The research sheds light on the mechanism behind the relationship between childhood trauma and mental disorders. Understanding how stress hormones affect astrocytes and synapse removal could lead to new strategies for preventing and treating mental health conditions.
More about Childhood Trauma
- Immunity Journal: Immunity, the international journal where the research was published.
- KAIST Department of Biological Sciences: The department at KAIST responsible for leading the research.
- National Research Foundation of Korea: The organization providing support for the research.
- Korea Health Industry Development Institute (KHIDI): Providing funding and resources for the research.
- Korea Dementia Research Center (KDRC): Contributing to the research effort in understanding mental health issues.
