P2-092 Aberrant activation of CDK5 triggers events leading to Alzheimer's pathology

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment, associated with a reduced concentration of acetylcholine (ACh) in brain cortex and hippocampus. Recently we reported that the N-acetylcysteine (NAC) decreases brain acetylcholinesterase (AChE) activity in vitro. Thus, the aim of the current study was to investigate the effect of NAC against streptozotocin (STZ) induced AD in mice. Mice were divided into four groups: I) Sham, II) NAC, III) STZ and IV) NAC + STZ. Animals were daily treated with NAC (50 mg/kg/day, p.o.) for nine consecutive days and with STZ (2.5 mg/kg i.c.v.) at the first and third days. Step down passive avoidance (SDPA, days 7–8) and Morris water maze (MWM, days 6–9) task were assessed to evaluate learning and memory. On the tenth day animals were euthanized for AChE and butyrylcholinesterase (BChE) activities and ACh, energy-rich phosphate and brain glucose uptake levels evaluations. A learning and memory impairment was observed in SDPA and MWM in those animals that receive STZ. Nevertheless, the same was not observed in those animals that also received NAC. Brain cortex and hippocampus AChE and hippocampus BChE activities increase induced by STZ were also prevented by NAC treatment. The STZ induced a brain energy metabolism imbalance, decreasing adenosine triphosphate and increasing adenosine levels. The glucose uptake decrease in hippocampus was prevented by NAC. In conclusion, NAC treatment prevented the cognitive disturbance, by restoring the cholinergic system and brain energy metabolism disorders. NAC could modulate cholinergic imbalance without causing any changes per se in the same.