title: N-acetylcysteine protects memory decline induced by streptozotocin in mice.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Laboratory of Biochemistry and Toxicology, Center of Natural and Exact Sciences, Federal University of Santa Maria, UFSM Campus, Santa Maria, RS, Brazil.
authors.forename: Michael
authors.initials: M
authors.lastname: Costa
authors.affiliation: Department of Biochemistry and Molecular Biology, Laboratory of Biochemistry and Toxicology, Center of Natural and Exact Sciences, Federal University of Santa Maria, UFSM Campus, Santa Maria, RS, Brazil.
authors.forename: Jamile
authors.initials: J
authors.lastname: Bernardi
authors.affiliation: Department of Biochemistry and Molecular Biology, Laboratory of Biochemistry and Toxicology, Center of Natural and Exact Sciences, Federal University of Santa Maria, UFSM Campus, Santa Maria, RS, Brazil.
authors.forename: Tiago
authors.initials: T
authors.lastname: Fiuza
authors.affiliation: Department of Biochemistry and Molecular Biology, Laboratory of Biochemistry and Toxicology, Center of Natural and Exact Sciences, Federal University of Santa Maria, UFSM Campus, Santa Maria, RS, Brazil.
authors.forename: Lidiane
authors.initials: L
authors.lastname: Costa
authors.affiliation: Department of Pharmaceutical Sciences, Center of Health Sciences, Federal University of Pernambuco, UFPE Campus, Recife, PE, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Brandão
authors.affiliation: Department of Biochemistry and Molecular Biology, Laboratory of Biochemistry and Toxicology, Center of Natural and Exact Sciences, Federal University of Santa Maria, UFSM Campus, Santa Maria, RS, Brazil. Electronic address: pereirame@yahoo.com.br.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Pereira
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000111:Acetylcysteine / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D004734:Energy Metabolism / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D013311:Streptozocin / Q000633:toxicity*
chemical_list: D018696:Neuroprotective Agents; D013311:Streptozocin; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D000111:Acetylcysteine
keywords: Acetylcholine; Behavioral; Cholinesterases; Cognition