Stress-inducible WASF3 regulates brain metabolism and cognitive function.

WASF3 overexpression in mouse hippocampus disrupts respiratory complex IV, shifts metabolism toward glycolysis, and induces a hypometabolic state linked to impaired learning.

• Why it matters: Cognitive impairment is a hallmark of ME/CFS, and WASF3 is induced with endoplasmic reticulum stress and disrupts mitochondrial respiration, suggesting a brain mechanism for “brain fog.”
• What they did: Using WASF3 transgenic and knockout mouse models, the study tested hippocampal overexpression and deficiency, measuring mitochondrial respiration, ATPIF1 levels, and learning under stress.
• The result: Increased WASF3 reduced ATPIF1 and impaired learning, while WASF3 deficiency increased ATPIF1, enhanced oxidative metabolism, and preserved cognitive function under stress.