Comparison between a Phoneutria nigriventer toxin treatment and galantamine treatment in a memory deficit mouse model

Abstract

Acetylcholine modulates circuits related to cognitive functions (attention, cognitive flexibility, memory, and social interaction). Consequences of low acetylcholine levels in cholinergic synaptic clefts include memory and sociability impairments. VAChT KDHET mice exhibit diminished vesicular acetylcholine transporter protein production, which could evoke low acetylcholine quantal release and memory and sociability issues. It has been demonstrated that the PhKv toxin, isolated from the Phoneutria nigriventer (Brazilian wandering spider) venom, inhibits the enzyme responsible for acetylcholine hydrolysis, acetylcholinesterase. This could result in acetylcholine remaining longer in the synaptic cleft, as well as alleviating cognitive problems caused by low levels of this neurotransmitter. Hence, here we intended to investigate VAChT KDHET mice cognitive deficits in a behavioral assay - the novel object recognition task - and examine the potential effect of the PhKv toxin in memory improvement of this mouse model. First, we noted that VAChT KDHET mice showed impaired object recognition memory. We also observed that these deficits, especially those related to short-term memory in the behavioral test, are sex-related. Subsequently, to assess the effects of PhKv toxin in object recognition memory, we injected PhKv or galantamine in VAChT KDHET mice and compared their performance in the novel object recognition task. We noted that mice treated with PhKv performed similarly to mice treated with galantamine or both vehicles in this behavioral assay. Finally, we observed that mice treated with both vehicles displayed memory improvements compared to non-treated (naive) mutant mice. Together, our results imply that PhKv may have an effect on memory improvement, which might be further explored to elucidate its mechanisms of action.