Surgery in aged mice suppresses acetylcholine release from septal neurons to the hippocampus, impairing memory and neurogenesis. Restoring this cholinergic pathway through pharmacological or sustained neural activation reverses both cognitive and regenerative deficits, pointing to a tractable mechanism underlying postoperative cognitive dysfunction.
Key Points
- Surgery reduces acetylcholine signaling in hippocampal memory circuits of aged mice
- Galantamine and sustained cholinergic pathway activation restore memory and neurogenesis
- Cholinergic restoration requires sustained activation, not acute stimulation alone
Longevity Analysis
Postoperative cognitive dysfunction represents a converging failure of neural signaling and cellular regeneration—two processes that determine cognitive resilience in aging. This work isolates a specific cholinergic circuit whose dysfunction after surgical stress impairs both memory encoding and the brain's capacity to generate new neurons. The finding suggests that protecting or restoring acetylcholine availability during and after surgical stress could preserve cognitive function in older adults, where neurogenesis and cholinergic tone naturally decline. Since the intervention works through sustained pathway activation rather than acute stimulation, implementation requires consistent cholinergic support—either pharmacologic or via pre- and post-operative protocols that stabilize this circuit.
Original published by Wiley Aging Cell, by Lei Lei, Qingsheng Meng, Xiaoyu Hu, Jinjin Yang, Ni Du, Songxue Su, Kenji Hashimoto, Jing Cao, Jian‐jun Yang .