Brain enzyme contributes to memory problems after surgery in mice
Experiments in mice aged 18–20 months implicated an enzyme in brain support cells in male-specific memory problems during the week after surgery.
Our read
Mechanisms- Studied:
- Experiments in mice
- In the record:
- One of 20 papers on abdominal surgery on record: 3 with results in people, 2 in animals.
- Why it’s aging research:
- Old against young, or naturally aged tissue.
Editor of record: Boris Djordjevic · AgingResearch.News
Experiments in male and female C57BL/6J mice aged 18–20 months compared abdominal surgery with anesthesia alone. Memory testing began two days later. Surgery impaired memory for objects and locations in males, but not females. It also reduced fluid entry into the hippocampus, a brain region involved in memory, in males.
These changes accompanied increased activity of glutamate carboxypeptidase II (GCPII), an enzyme in astrocytes, or brain support cells. Glutamate, a chemical messenger between nerve cells, also accumulated in males. Reducing GCPII production specifically in hippocampal astrocytes 21 days before surgery improved memory and restored fluid entry. A drug that inhibits GCPII also improved memory and reduced glutamate buildup. The authors identified disrupted glutamate regulation by this enzyme as a mechanism contributing to male-specific vulnerability to memory problems after surgery.
Why it matters
Cognitive problems after surgery are a concern in older people. This work addresses how brain support cells may contribute to the aging brain’s vulnerability.
Caveats
These mouse experiments do not establish benefits in people. The enzyme-targeting experiments involved only males, and tracer entry measured fluid influx rather than waste clearance.
- Abdominal surgery
- Glutamate carboxypeptidase II inhibitor
- FOLH1
- Glutamate
- Perioperative neurocognitive disorder
- Mice
The paper
Johns Hopkins University
Alzheimer's & Dementia, Jul 2026, Open access
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