Anesthesia and surgery induce sex-dependent Tau phosphorylation and behavior changes in aged mice

Area of Science:

• Neuroscience
• Gerontology
• Endocrinology

Background:

• Preoperative blood Tau phosphorylated at threonine 217 (Tau-PT217) is an Alzheimer's disease biomarker associated with postoperative delirium.
• Anesthesia/surgery increases Tau-PT217 and can cause behavioral changes, but sex-dependent effects are unclear.

Purpose of the Study:

• To investigate the sex-dependent effects of anesthesia/surgery on Tau-PT217 levels and postoperative behavior in aged mice.
• To explore the role of testosterone and androgen receptor signaling in these sex-dependent changes.

Main Methods:

• Aged male and female mice underwent abdominal surgery under general anesthesia.
• Tau-PT217, inflammatory markers, and GSK3β activity were measured in tissues and blood.
• Behavioral tests assessed delirium-like symptoms.
• Hormonal manipulations (orchiectomy, enzalutamide, testosterone inhalation) were performed.

Main Results:

• Anesthesia/surgery elevated Tau-PT217 and caused delirium-like behavior in aged females, but not males.
• These changes were linked to higher inflammatory markers and GSK3β activity in females.
• Testosterone manipulation in males and females altered Tau-PT217 levels and behavior, suggesting a sex-dependent mechanism.

Conclusions:

• Testosterone and androgen receptor signaling significantly influence sex-dependent differences in Tau phosphorylation.
• These hormonal pathways may underlie anesthesia/surgery-induced Tau changes and postoperative behavioral alterations in aged mice.