title: Impaired cognitive performance in neuronal nitric oxide synthase knockout mice is associated with hippocampal protein derangements.
abstract: Nitric oxide is implicated in modulation of memory and pharmacological as well as genetic inhibition of neuronal nitric oxide synthase (nNOS) leads to impaired cognitive function. We therefore decided to study learning and memory functions and cognitive flexibility in the Morris water maze (MWM) in 1-month-old male mice lacking nNOS (nNOS KO). Hippocampal protein profiling was carried out to possibly link protein derangement to impaired cognitive function. Two-dimensional gel electrophoresis with in-gel digestion of spots and subsequent MALDI-TOF identification of proteins and quantification of proteins using specific software was applied. In the memory as well as in the relearning task of the MWM, most of the nNOS KO failed to find the submerged platform within a given time. Proteomic evaluation of hippocampus, the main anatomical structure computing cognitive functions, revealed aberrant expression of a synaptosomal associated protein of the exocytotic machinery (NSF), glycolytic enzymes, chaperones 78 kDa glucose-regulated protein, T-complex protein 1; the signaling structure guanine nucleotide-binding protein G(I)/G(S)/G(T) and heterogeneous nuclear ribonucleoprotein H of the splicing machinery. We conclude that nNOS knockout mice show impaired spatial performance in the MWM, a finding that may be either linked to direct effects of nNOS/NO and/or to specific hippocampal protein derangements.
authors.affiliation: Department of Neonatology, University of Vienna, Währinger Gürtel 18, A 1090 Vienna, Austria.
authors.forename: Liselotte
authors.initials: L
authors.lastname: Kirchner
authors.forename: Rachel
authors.initials: R
authors.lastname: Weitzdoerfer
authors.forename: Harald
authors.initials: H
authors.lastname: Hoeger
authors.forename: Angelika
authors.initials: A
authors.lastname: Url
authors.forename: Peter
authors.initials: P
authors.lastname: Schmidt
authors.forename: Mario
authors.initials: M
authors.lastname: Engelmann
authors.forename: Santiago Rosell
authors.initials: SR
authors.lastname: Villar
authors.forename: Michael
authors.initials: M
authors.lastname: Fountoulakis
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
authors.forename: Barbara
authors.initials: B
authors.lastname: Lubec
mesh_terms: D000818:Animals; D003071:Cognition / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I
chemical_list: D009419:Nerve Tissue Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse