Nicotine Induced Neurocognitive Protection and Anti-inflammation Effect by Activating α4β2 Nicotinic Acetylcholine Receptors in Ischemic Rats

Introduction: The main objective of this study was to explore the mechanism of nicotine improving cognitive impairments in ischemic rats. Methods: Twenty adult male Sprague-Dawley (SD) rats underwent ischemic model surgery by injecting endothelin- 1 into the left thalamus, which were classified into four different groups with different intervention: nicotine (1.5 mg/kg/d), dihydro-beta-erythroidine (DH beta E; 3 mg/kg/d), nicotine (1.5 mg/kg/d) + DH beta E (3 mg/kg/d), or saline, after ischemic model surgery. Another five male SD rats also underwent same surgery, while not injecting endothelin-1 but saline, as the control group. Morris water maze (MWM) test was adopted to assess the cognition. All the rats underwent the MWM test, micro positron emission tomography imaging with 2-[F-18]-A-85380, and messenger RNA (mRNA) test of alpha(4) nicotinic acetylcholine receptor (nAChR), beta(2) nAChR, tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, and IL-6. Results: The MWM test showed the rats given nicotine showing better memory than ischemic rats (p <.05), whereas the rats given DH beta E or both nicotine and DH beta E did not show any statistical difference from the ischemic rats (p >.05). Micro positron emission tomography imaging showed higher uptake of tracer in the left thalamus and whole brain in rats given nicotine than in ischemic rats, but the rats given DH beta E or both nicotine and DH beta E did not. By real-time PCR test, the mRNA of alpha(4) nAChR and beta(2) nAChR in rats given nicotine increased significantly compared with ischemic rats and decreased TNF-alpha, IL-1 beta, and IL-6 mRNA (all ps <.05). Conclusions: By activating alpha(4)beta(2) nAChRs, nicotine plays a role in inhibiting the inflammatory factors, which contributes to improving cognitive impairment in ischemic rats.