title: Decreased hippocampal homoarginine and increased nitric oxide and nitric oxide synthase levels in rats parallel training in a radial arm maze.
abstract: L-homoarginine (hArg) is derived from enzymatic guanidination of lysine. It was demonstrated that hArg is a substrate for nitric oxide (NO) synthesis, blocks lysine transport and inhibits the uptake of arginine into synaptosomes and modulates GABA responses ex vivo. As there is limited information on its physiological roles in the brain, the aim of the study was to show whether hippocampal or frontal lobe (FL) hArg is paralleling training in the radial arm maze (RAM) or NO formation. Hippocampi and FL of male Sprague-Dawley rats were taken from trained or yoked in a RAM. Then hArg and metabolites, NO and NO synthase (NOS) were determined by standard methods. The animals learned the task in the RAM showing significant reduction of working memory errors. hArg showed decreased levels in both brain regions of trained animals as compared to yoked animals. Nitrate plus nitrite (NOx) concentrations and NOS activity were significantly increased in hippocampi, F(1,36) = 170.5; P ≤ 0.0001 and FL, F(1,36) = 74.67; P ≤ 0.0001 of trained animals as compared to yoked animals. Levels of hArg were negatively correlated with NOx in hippocampus (r = -0.6355; P = 0.0483) but not in FL and with lysine in the FL (r = -0.6650; P = 0.0358). NOx levels were positively correlated with NOS in both the hippocampus (r = 0.7474; P = 0.0129) and FL (r = 0.9563; P ≤  0.0001). These novel findings indicate that hArg is linked to NO formation in hippocampus but not in FL and is paralleling spatial memory in the RAM.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Room 212, Kleberg Bldg., Althanstraße 14, 1090, Vienna, Austria.
authors.forename: Ajinkya
authors.initials: A
authors.lastname: Sase
authors.affiliation: Departments of Animal Science and Medical Physiology, Texas A&M University, 2471 TAMU, College Station, TX, 77843-2471, USA.
authors.forename: Gayan
authors.initials: G
authors.lastname: Nawaratna
authors.affiliation: Departments of Animal Science and Medical Physiology, Texas A&M University, 2471 TAMU, College Station, TX, 77843-2471, USA.
authors.forename: Shengdi
authors.initials: S
authors.lastname: Hu
authors.affiliation: Departments of Animal Science and Medical Physiology, Texas A&M University, 2471 TAMU, College Station, TX, 77843-2471, USA. g-wu@tamu.edu.
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Room 212, Kleberg Bldg., Althanstraße 14, 1090, Vienna, Austria. gert.lubec@univie.ac.at.
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000378:metabolism*; D006709:Homoarginine / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000502:physiology
chemical_list: D006709:Homoarginine; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat
keywords: Hippocampus; Homoarginine; Nitric oxide; Radial arm maze; Spatial memory