title: Pre-aggregated Aβ(25-35) alters arginine metabolism in the rat hippocampus and prefrontal cortex.
abstract: Amyloid beta (Aβ) has been proposed to play a central and causative role in the development of Alzheimer's disease. Aβ(25-35), the neurotoxic domain of the full-length Aβ, causes learning and memory impairments in rodents. The present study investigated the effects of a single bilateral i.c.v. infusion of pre-aggregated Aβ(25-35) (30 nmol/rat) on animals' performance in the open field, and on arginine metabolic enzymes and metabolites in the CA1, CA2/3, and dentate gyrus (DG) sub-regions of the hippocampus and prefrontal cortex (PFC) at the time point of 6-8 days after Aβ infusion. Aβ(25-35) rats displayed reduced exploratory activity in the open field relative to the Aβ(35-25) (reverse peptide; 30 nmol) rats. Aβ(25-35) resulted in significantly decreased nitric oxide synthase (NOS) activity and endothelial NOS protein expression, but increased arginase activity, arginase II protein expression, and ornithine and putrescine levels, in hippocampal CA2/3. There were increased glutamate and putrescine levels in the DG, but decreased agmatine levels in the DG and PFC, in the Aβ(25-35) group relative to the Aβ(35-25) one. Cluster analyses were performed to determine if the nine related neurochemical variables (arginine, citrulline, ornithine, agmatine, putrescine, spermidine, spemine, glutamate, and GABA) formed distinct groups, and whether it changed as a function of Aβ(25-35). There were substantially different clusters between the two groups in the hippocampus and PFC. These results demonstrate that Aβ(25-35) alters arginine metabolism, which further supports the prominent role of arginine and its metabolites in Alzheimer's disease (AD) pathogenesis.
authors.affiliation: Department of Anatomy and Structural Biology, University of Otago, Dunedin, New Zealand. ping.liu@otago.ac.nz
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Jing
authors.forename: Nicola D
authors.initials: ND
authors.lastname: Collie
authors.forename: Saskia A
authors.initials: SA
authors.lastname: Campbell
authors.forename: Hu
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods; D016000:Cluster Analysis; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology / Q000633:toxicity*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D053719:Tandem Mass Spectrometry
chemical_list: D000596:Amino Acids; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C113041:amyloid beta-protein (35-25); D001120:Arginine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III