Activation of cholinergic system partially rescues olfactory dysfunction-induced learning and memory deficit in mice

Deficits in olfaction are associated with neurodegenerative disorders such as Alzheimer's disease. A recent study reported that intranasal zinc sulfate (ZnSO₄)-treated mice show olfaction and memory deficits. However, it remains unknown whether olfaction deficit-induced learning and memory impairment is associated with the cholinergic system in the brain. In this study, we evaluated olfactory function by the buried food find test, and learning and memory function by the Y-maze and passive avoidance tests in ZnSO₄-treated mice. The expression of choline acetyltransferase (ChAT) protein in the olfactory bulb (OB), prefrontal cortex, hippocampus, and amygdala was assessed by western blotting. Moreover, we observed the effect of the acetylcholinesterase inhibitor physostigmine on ZnSO₄-induced learning and memory deficits. We found that intranasal ZnSO₄-treated mice exhibited olfactory dysfunction, while this change was recovered on day 14 after treatment. Both short-term and long-term learning and memory were impaired on days 4 and 7 after treatment with ZnSO₄, whereas the former, but not the latter, was recovered on day 14 after treatment. A significant correlation was observed between olfactory function and short-term memory, but not long-term memory. Treatment with ZnSO₄ decreased the ChAT level in the OB on day 4, and increased and decreased the ChAT levels in the OB and hippocampus on day 7, respectively. Physostigmine improved the ZnSO₄-induced deficit in short-term, but not long-term, memory. Taken together, the present results suggest that short-term memory may be closely associated with olfactory function via the cholinergic system.