title: Neopterin acts as an endogenous cognitive enhancer.
abstract: Neopterin is found at increased levels in biological fluids from individuals with inflammatory disorders. The biological role of this pteridine remains undefined; however, due to its capacity to increase hemeoxygenase-1 content, it has been proposed as a protective agent during cellular stress. Therefore, we investigated the effects of neopterin on motor, emotional and memory functions. To address this question, neopterin (0.4 and/or 4pmol) was injected intracerebroventricularly before or after the training sessions of step-down inhibitory avoidance and fear conditioning tasks, respectively. Memory-related behaviors were assessed in Swiss and C57BL/6 mice, as well as in Wistar rats. Moreover, the putative effects of neopterin on motor and anxiety-related parameters were addressed in the open field and elevated plus-maze tasks. The effects of neopterin on cognitive performance were also investigated after intraperitoneal lipopolysaccharide (LPS) administration (0.33mg/kg) in interleukin-10 knockout mice (IL-10(-/-)). It was consistently observed across rodent species that neopterin facilitated aversive memory acquisition by increasing the latency to step-down in the inhibitory avoidance task. This effect was related to a reduced threshold to generate the hippocampal long-term potentiation (LTP) process, and reduced IL-6 brain levels after the LPS challenge. However, neopterin administration after acquisition did not alter the consolidation of fear memories, neither motor nor anxiety-related parameters. Altogether, neopterin facilitated cognitive processes, probably by inducing an antioxidant/anti-inflammatory state, and by facilitating LTP generation. To our knowledge, this is the first evidence showing the cognitive enhancer property of neopterin.
authors.affiliation: Laboratório de Bioenergética e Estresse Oxidativo - LABOX, Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
authors.forename: Karina
authors.initials: K
authors.lastname: Ghisoni
authors.affiliation: Laboratório de Bioenergética e Estresse Oxidativo - LABOX, Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
authors.forename: Aderbal S
authors.initials: AS
authors.lastname: Aguiar
authors.affiliation: Departamento de Farmacologia, Universidade Federal de Santa Catarina, Campus Trindade, Florianópolis, SC 88049-900, Brazil.
authors.forename: Paulo Alexandre
authors.initials: PA
authors.lastname: de Oliveira
authors.affiliation: Departamento de Farmacologia, Universidade Federal de Santa Catarina, Campus Trindade, Florianópolis, SC 88049-900, Brazil.
authors.forename: Filipe Carvalho
authors.initials: FC
authors.lastname: Matheus
authors.affiliation: Departamento de Farmacologia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, IFEC-CONICET, Córdoba, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Gabach
authors.affiliation: Departamento de Farmacologia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, IFEC-CONICET, Córdoba, Argentina.
authors.forename: Mariela
authors.initials: M
authors.lastname: Perez
authors.affiliation: Instituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Valeria P
authors.initials: VP
authors.lastname: Carlini
authors.affiliation: Institut Pasteur de Montevideo, Montevideo, Uruguay.
authors.forename: Luis
authors.initials: L
authors.lastname: Barbeito
authors.affiliation: INSERM UMR S894, Centre de Psychiatrie et Neurosciences, Paris 75014, France; Université Paris Descartes EA 4475, Paris 75005, France.
authors.forename: Raymond
authors.initials: R
authors.lastname: Mongeau
authors.affiliation: INSERM UMR S894, Centre de Psychiatrie et Neurosciences, Paris 75014, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Lanfumey
authors.affiliation: Departamento de Farmacologia, Universidade Federal de Santa Catarina, Campus Trindade, Florianópolis, SC 88049-900, Brazil.
authors.forename: Rui Daniel
authors.initials: RD
authors.lastname: Prediger
authors.affiliation: Laboratório de Bioenergética e Estresse Oxidativo - LABOX, Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil. Electronic address: alatini@ccb.ufsc.br.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Latini
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects*; D005239:Fear / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D007266:Inhibition, Psychological; D007276:Injections, Intraventricular; D016753:Interleukin-10; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D000069077:Memory Consolidation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019798:Neopterin / Q000008:administration & dosage / Q000494:pharmacology*; D018697:Nootropic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C556062:IL10 protein, mouse; D018697:Nootropic Agents; D016753:Interleukin-10; D019798:Neopterin
keywords: Learning and memory; Neopterin; Neuroinflammation