the influence of α₄β_{2 nAChRs ischemic cognitive impairment in rats and the expression of inflammatory cytokines}

Objectives: The nicotinic acetylcholine system plays a important role in the mediation of memory learing,drug addiction,and control of pain.nAChRs play important roles in ischemic damage,and intracerbral hemorrhage.The mechanism responds to the modulation of macrophage/microglia activation by nAChRs receptors and its activation has been related to the suppression of the inflammation.The present study investigated the activation of α₄β₂ nAChRs attenuates endothelin-1-induced ischemic cognitive deficits in thalamus and its involvement in inflammatory reaction.

Methods: Adult male Sprague-Dawley rats were administrated endothelin-1 in thalamus through brain stereotactic apparatus. Then nicotine(1.5mg/kg/d, s.c), the α₄β₂ nAChRs antagonist dihydro-β-erythroidine hydrobromide (DHβE,3mg/kg/d,s.c), and saline with the same dose were administrated after the surgery for 9 days. The shame operation group(received saline administrated in thalamus) were administrated subcutaneous injection of the same dose saline. The Morris Water Maze(MWM) was performed for 6 days in the fourth day after nicotine or saline exposured. 2-[¹⁸F]-A-85380MicroPET imaging was performed to assess the density of α₄β₂ nAChRs in different brain domains on the following day. The expression of inflammatory cytokines including IL-1β,IL-6,TNF-α and the nicotinic acetylcholine receptor α₄ and β₂through the real time PCR.

Results: The Morris water maze showed that The escape latency of all the groups more and more shorten with the increase of experimental days,the difference between ischemia group and nicotine treatment group were statistically significant, while compared with DHβE treatment group, there was no statistically significant. And at the sixth day,the times of crossing the platform quadrant in ischemia group and nicotine treatment group were statistically significant.MicroPET imaging was performed after 120 min when tracer 2-[18F]-A-85380 injection, the result showed that the α4β2 nicotinic acetylcholine receptor were up-regulated in the in the thalamus ischemic rat, and the expressed of IL-1β,IL-6,TNF-α were reduced through the real time PCR verified. When the rat were treated with the DHβE,the the expression of inflammatory cytokines were up-regulated ,but the α4β2 nicotinic acetylcholine receptor were lower than the nicotinic treatment group and ischemia group.

Conclusion: The activation of α₄β₂ nicotinic acetylcholine receptor have a key role in the inflammatory reaction underlying ischemic cognitive deficits in thalamus. Research Support: National Natural Science Foundation of China (81000623, 81671717)