α7 Nicotinic Acetylcholine Receptor May Be a Pharmacological Target for Perioperative Neurocognitive Disorders

Background: The alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) is a promising therapeutic target in neurodegenerative diseases. This study examined the effects of surgery and anesthesia on alpha 7nAChR expression in the central nervous system and determined the mechanisms by which alpha 7nAChR mediates neuroprotection in perioperative neurocognitive disorders (PNDs) in aged mice. Methods: Eighteen-month-old male C57BL/6J mice underwent aseptic laparotomy under isoflurane anesthesia, maintaining spontaneous ventilation to establish the PNDs model. Agonists and antagonists of the alpha 7nAChR and tropomyosin receptor kinase B (TrkB) receptors were administered before anesthesia. The alpha 7nAChR expression, peripheral as well as hippocampal interleukin-1 beta (IL-1 beta), and the brain-derived neurotrophic factor (BDNF) levels were assessed. Separate cohorts of aged mice were tested for cognitive decline using the Morris water maze (MWM). Results: Surgery and anesthesia significantly suppressed alpha 7nAChR expression in the hippocampus and cortex. Surgery-induced IL-1 beta upregulation in the serum as well as hippocampus and hippocampal microglial activation were reversed by the alpha 7nAChR agonist. A significant reduction in the hippocampal BDNF levels were also observed. The alpha 7nAChR stimulation reversed, and alpha 7nAChR suppression promoted BDNF reduction in the hippocampus. Blocking the BDNF/TrkB signaling pathway abolished alpha 7nAChR-induced neuroprotection in PNDs, as evidenced by poor cognitive performance in the MWM test. Conclusions: These data reveal that alpha 7nAChR plays a key role in PNDs. The mechanisms of the anti-inflammatory pathway and BDNF/TrkB signaling pathways are involved in alpha 7nAChR-meidiated neuroprotection in PNDs.