Abstract
Butyrylcholinesterase (BChE) is an important enzyme for detoxication and metabolism of ester compounds.It also hydrolyzes the neurotransmitter acetylcholine (ACh) in pathological conditions and may play a role in Alzheimer’s disease (AD). We here compared the learning ability and vulnerability to AB toxicity in male and female BChE knockout (KO) mice and their 129 Sv wild-type (Wt) controls. Animals tested for place learning in the water-maze showed increased acquisition slopes and presence in the training quadrant during the probe test. An increased passive avoidance response was also observed for males. BChE KO mice therefore showed enhanced learning ability in spatial and non-spatial memory tests. Intracerebroventricular (ICV) injection of increasing doses of amyloid-B[25–35] (AB25–35) peptide oligomers resulted, in Wt mice, in learning and memory deficits, oxidative stress and decrease in ACh hippocampal content. In BChE KO mice, the AB25–35-induced deficit in place learning was attenuated in males and blocked in females. No change in lipid peroxidation or ACh levels was observed after AB25–35 treatment in male or female BChE KO mice. These data showed that the genetic invalidation of BChE inmice augmented learning capacities and lowered the vulnerability to AB toxicity.