Neopterin acts as an endogenous cognitive enhancer

KARINA GHISONI; RUI PREDIGER; VALERIA P. CARLINI; LAURENCE LANFUMEY; PAULO ALEXANDRE DE OLIVEIRA; MARIELA F. PÉREZ; ADERBAL AGUIAR; FILIPE CARVALHO MATHEUS; LAURA GABACH; LUIZ BARBEITO; ALEXANDRA LATINI

BRAIN BEHAVIOR AND IMMUNITY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2016 vol. 56 p. 156 - 164

0889-1591

Neopterin, a byproduct of the tetrahydrobiopterin de novo pathway, is found at increased levels in biological fluids from individuals affected by inflammatory disorders. The role of this pteridine in still not defined, however due to its capacity to increase hemeoxygenase-I content, it was proposed a cytoprotective activity, during cellular stress. Therefore, in order to understand better its effect in in vivo systems, we investigated the effect of neopterin on cognition. To address this, neopterin (0.4 and/or 4 pmol) was injected intracerebroventricularly before or after the acquisition sessions in step-down and fear conditioning tests, respectively, and avoidance or fear memories were, assessed in Swiss and VGV (mice with fully edited isoform of the serotonin receptor subtype 2C) mice, and Wistar rats. The effect of neopterin on memory was also investigated under an inflammatory state induced by intraperitoneal lipopolysaccharide administration (0.33 mg/kg) in IL-10(-/-). It was consistently observed though the different species of rodents 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 long-term potentiation (LTP) process in hippocampus, and reduced levels of IL-6, after the LPS challenge. However, neopterin administration after acquisition did not alter the consolidation of fear memories. In conclusion, neopterin facilitated the cognitive process, by probably favoring an antioxidant and anti-inflammatory environments and facilitating LTP generation. To our knowledge, these are the firsts evidences demonstrating that an endogenous pteridine enhances cognition.