research model
[충청뉴스 이성현 기자] A research team in Korea has identified for the first time the cause of the onset of mental illness that can come from experiencing stressful situations such as child abuse in childhood.
The Korea Advanced Institute of Science and Technology (KAIST) announced on the 1st that a research team led by Professor Jeong Won-seok of the Department of Life Sciences was the first to identify that mental illness caused by stress in childhood, such as child abuse and neglect, is caused by excessive synapse removal in astrocytes.
Although it has been clinically known that excessive stress can act as a cause of various mental disorders, the exact pathogenesis is not known, so this study is expected to be greatly applied to the prevention and treatment of stress-induced mental disorders.
The research team conducted clinical drug screening approved by the US Food and Drug Administration (FDA) to discover a new mechanism that regulates the role of astrocytes in consuming and removing foreign substances (phagocytosis).
As a result, they found that synthetic glucocorticoids, called stress hormones, abnormally greatly increase the phagocytosis of astrocytes.
Glucocorticoids play necessary roles in maintaining life, such as sugar metabolism and anti-inflammation, while secreting them by external stimuli such as stress, allowing the body to respond.
However, excessive long-term exposure to glucocorticoids due to chronic stress can lead to the development of various psychiatric disorders such as depression, cognitive impairment, and anxiety symptoms.
The research team used a childhood social deficit mouse model to understand the functional changes of astrocytes caused by childhood stress. It was found that the expression of the receptor called was greatly increased.
Through increased MERTK, astrocytes selectively engulfed and reduced excitatory synapses of specific neurons present in various cerebral cortices, resulting in the formation of abnormal neural networks, resulting in complex behavioral abnormalities such as social deficits and depression later in adulthood. found
In addition, the research team observed that microglia, known to play an important role in brain immune function along with astrocytes, do not participate in synapse elimination in the childhood social deficit mouse model.
This confirms that astrocytes, not microglial cells, specifically respond to stress hormones to regulate the brain environment in childhood stress situations.
The research team used brain organoids derived from human induced pluripotent stem cells to check the response to stress hormones to see if these findings could be applied to humans.
The research team also found that both glucocorticoid receptors and phagocytic receptors of astrocytes were activated by stress hormones in human brain organoids, and also confirmed that astrocytes excessively remove excitatory synapses.
Professor Won-Seok Won said, “Although the mechanism of childhood stress and brain disease development has not been well understood, this study proves for the first time that excessive phagocytosis of astrocytes can be an important factor in the development of mental diseases.” In the understanding and treatment of various brain diseases, the regulation of immune function of astrocytes can be applied as a fundamental target.”
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2023-08-01 00:59:34
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