Stress hormones drive female-specific brain rewiring following ketamine anesthesia

A recent study published in Science Advances has revealed a surprising sex-specific response in female mice following ketamine anesthesia. Unlike males, female mice exhibited a surge in stress hormone levels during recovery, which triggered immune cells in the brain called microglia to rewire neuronal connections. This finding suggests profound differences in how the brain regains function after anesthesia, with sex playing a critical role.

Ketamine, a unique anesthetic that induces juvenile-like plasticity in the brain, has been shown to induce mild anxiety in female animals, aligning with other studies demonstrating sex differences in anesthesia responses. Microglia, the brain's resident immune cells, were found to behave differently between male and female mice during anesthesia recovery.

After administering ketamine, female mice demonstrated increased microglial activity and altered physical shape, forming prolonged contacts with nearby neurons. These cellular changes led to increased electrical activity in female neurons, indicating enhanced neural plasticity and synaptic function. The researchers discovered that female microglia selectively increased the expression of a gene called Fkbp5, which produces a protein involved in the body's response to stress hormones, particularly corticosterone.

Blood tests confirmed that female mice had nearly three times higher corticosterone levels two hours after ketamine injection compared to males. Blocking the adrenal glands, which produce corticosterone, in female mice prevented the ketamine-induced changes in microglial activity and neuron interaction. When corticosterone was directly injected, the changes were rapidly restored.

While these findings shed light on the sex-specific effects of ketamine anesthesia, the researchers caution that the study was conducted on mice and further investigations are needed to determine if the results translate to human patients. The dosage and method of ketamine administration used in the experiment differed from those typically used in psychiatry, and the long-term persistence of the observed neural connections remains unclear.