Understanding Factors that Protect the Brain During Stress

Illustration of a person’s silhouette with the brain area colored in red, yellow, and green. The background behind the person is a series of connected lines that intersect at circles.

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The brain, particularly the hippocampus, is sensitive to high levels of stress hormones called glucocorticoids that are released under stressful or traumatic circumstances. A key question for researchers is identifying how the brain protects itself from stress-related damage or cell death.

The Loh Lab reported findings on how hippocampal CA3 neurons, which regulate cognitive functions like learning and memory, are protected from stress. Using mouse models, the study team tested the importance of two neuroprotective proteins called brain-derived neurotrophic factor (BDNF) and carboxypeptidase E (CPE). CPE is also known as neurotrophic factor α-1, or NFα-1.

The study team found that CPE/NFα-1, not BDNF, is essential to protect neurons from severe stress. Their findings suggest that BDNF is likely more important in protecting neurons during milder types of stress. They also found that the protective effect of CPE/NFα-1 does not rely on the protein’s enzymatic activity.

Overall, this research provides foundational knowledge that scientists can use to develop treatments for neurodegenerative diseases, which occur when neurons are damaged or die prematurely. For example, drugs that can stimulate the production of CPE/NFα-1, such as rosiglitazone, could potentially protect neurons and prevent or delay disease progression. More research is needed to explore these ideas.

Learn more about the Neurosciences Group: https://www.nichd.nih.gov/about/org/dir/affinity-groups/neurosciences.

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