DEPRESSION, ANXIETY: Discovery of a master molecule of the stress response

The study is conducted on zebrafish, a vertebrate whose genetics have much in common with humans and which is a recognized model for studying the functioning and dysfunction of the human brain. In zebrafish, the system that controls stress responses begins to develop 1-2 days after fertilization, and stress-induced cortisol signals can be seen as early as 4-5 days after fertilization. Its rapid development, combined with its translucency, make zebrafish a study model of choice for neuroscientists.

DSCAML1, apoptosis, cortisol and stress response

Scientists focused on the DSCAML1 molecule because genetic changes in its human equivalent are seen in patients with a wide range of mental health conditions, including intellectual disability, autism spectrum disorder (ASD), schizophrenia, epilepsy and stress. These brain development experts again identify, in zebrafish, the molecule DSCAML1 (DS cell adhesion molecule like 1) as essential for the development of the stress response:

  • And DSCAML1 deficiency disrupts brain development and increases levels of cortisol, making the well-known stress hormone unable or less able to do its job well in times of stress. In zebrafish with DSCAML1 deficiency, cortisol levels are 2 to 3 times higher than in the control group;
  • A deficiency in DSCAML1 disrupts the “cleaning” process of the brain: DSCAML1 seems to interact with the process of programmed cell death or apoptosiswhich rids the body of unnecessary cells, such as excessive production of neurons in the brain. “Thus, and especially during human development, cell death is an important function”, recalls the lead author, Dr. Pan, associate professor at the Fralin Biomedical Research Institute. Here, this cell death process is disrupted in zebrafish that are deficient in DSCAML1, confirming the key role of the molecule in the development of neurons that regulate stress.
  • Thus, DSCAML1 deficiency in zebrafish imbalances the stress response.

The researchers suggest that a better understanding of the process of cell death in a patient, by studying the different types of specific cells in the brain and by using high-resolution MRI or other imaging technologies could lead to a better understanding disease and places to target therapy. Beyond that, these works, although experimental, reveal a target of choice: DSCAML1.

Regulating DSCAML1 could restore a well-functioning stress response and reduce stress-related disorders such as anxiety and depression.

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