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A new study published in Cell Reports looked at early stress-induced impaired brain functioning.

“We were trying to figure out how the long-lasting, life-long adverse effects of transient early-life stress on behavioral and endocrine responses to adult stresses come about,” study author Tallie Z. Baram told us. “This is important, because these changes are tied to mental illnesses.”

More and more research is looking into adverse childhood experiences (ACEs) and how early trauma can affect the brain’s development, making those children more susceptible to mental health issues later in life. According to the Substance Abuse and Mental Health Services Administration, at least one traumatic event was indicated by more than two thirds of children by the time they turned age 16.

The types of traumatic events children can experience fall within the realm of psychological, sexual, and/or physical abuse. They can also be a result of a serious accident or life-threatening illness.

Researchers of the current study tested if the brain's immune cells might be involved. Their theory was that they might and they also thought it would be very difficult to show that in fixed brain tissue, so they aimed to look at the brain live.

“We looked at early stress-induced impaired microglial pruning of excitatory synpases on immature CRH-expressing neurons and how this may provoke aberrant adult stress responses,” Baram told us. “As you know, early-life adversity impacts more than 50 per cent of the world's children. This outcome is hugely important.”

The study found that the brain's immune cells, the microglia, function poorly in individuals exposed to early-life adversity/stress. During development, microglia prune unnecessary brain connections (synapses) leading to properly sculpted stress-responsive circuits.

“The poor function of the microglia during developmental stress led to too many synapses and aberrant responses to future stresses the adult,” Baram told us. “We know this is a causal role, because when we artificially activated microglia in stressed neonatal mice, this prevented the synapse excess and the abnormal responses to stress during adulthood.”

Researchers were surprised how specific the results were and that only microglia living next to stress-sensitive neurons were affected.

"We established how early-life adversity/stress enduringly changes behavioral and hormonal responses to further stresses during the lifetime," Baram told us. "These resulting aberrant stress-responses are thought to underlie/contribute to several major mental illnesses including depression.
We identified the role of microglia in this process. The next steps are to identify if the molecules that lead to microglial dysfunction can be used to prevent their malfunction in people."

Much of neuroscience and study of brain diseases has focused on the brain's neurons. This study highlights that in addition to neurons, other brain cells, and especially immune cells in the brain play crucial roles in brain health and disease. neuroimmune interactions are a novel, important avenue to understanding and treating several rain disorders, perhaps including alzheimer's in addition to mental illnesses.

The study was also authored by Jessica L. Bolton, Annabel K. Short, Shivashankar Othy, Marie-Eve Tremblay, Michael D. Cahalan, Cassandra L. Kooiker, Manlin Shao, Benjamin G. Gunn, Jaclyn Beck, Xinglong Bai, Stephanie M. Law, Julie C. Savage, Jeremy J. Lambert, and Delia Belelli. All the authors contributed equally and from the Neuroscience Institute, Center for Neuroinflammation and Cardiometabolic Diseases at Georgia State University in Atlanta.