Neopterin acts as an endogenous cognitive enhancer

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 4 pmol) 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 (0.33 mg/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. Fil: Ghisoni, Karina. Universidade Federal de Santa Catarina; Brasil Fil: Aguiar, Aderbal S.. Universidade Federal de Santa Catarina; Brasil Fil: Oliveira, Paulo Alexandre de. Universidade Federal de Santa Catarina; Brasil Fil: Matheus, Filipe Carvalho. Universidade Federal de Santa Catarina; Brasil Fil: Gabach, Laura. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina Fil: Perez, Mariela Fernanda. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina Fil: Carlini, Valeria Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina Fil: Barbeito, Luis. Instituto Pasteur de Montevideo; Uruguay Fil: Mongeau, Raymond. Université Paris Descartes. INSERM UMR. Centre de Psychiatrie et Neurosciences; Francia Fil: Lanfumey, Laurence. Umr S894, Centre de Psychiatrie Et Neurosciences; Francia Fil: Prediger, Rui Daniel. Universidade Federal de Santa Catarina; Brasil Fil: Latini, Alexandra. Universidade Federal de Santa Catarina; Brasil