Surgery impairs memory and brain cell regeneration in aged mice by disrupting cholinergic signaling from the medial septum to the hippocampus. Restoring this pathway through pharmacological or sustained neural activation reverses both cognitive and neurogenic deficits, suggesting a tractable mechanism for postoperative cognitive dysfunction.
Key Points
- Surgery suppresses acetylcholine release in hippocampal circuits critical to memory
- Galantamine restores memory and neurogenesis by potentiating cholinergic signaling
- Sustained pathway activation outperforms acute stimulation for cognitive recovery
Longevity Analysis
Postoperative cognitive dysfunction represents a preventable mechanism of accelerated cognitive aging in surgical populations. The identification of a discrete cholinergic circuit whose restoration rescues both memory performance and the regenerative capacity of hippocampal neurons establishes a biological target with clinical relevance. Age-related decline in cholinergic signaling is known to compromise learning and neuroplasticity; this work demonstrates that surgical stress amplifies this vulnerability and that restoring cholinergic tone can reverse the damage. For individuals facing surgical procedures, understanding and supporting this pathway may preserve cognitive reserve and maintain the brain's capacity for adaptive regeneration.
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 .