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.

Anthropometric Parameters in Celiac Disease: A Review on the Different Evaluation Methods and Disease Effects

“…More complex and expensive variables were used in smaller proportions in anthropometric studies involving patients with celiac disease: fat mass (FM) 53.6%, fat-free mass (FFM) 44.8%, bone mineral density (BMD) 46.4%, and bone mineral content (BMC) 9%. Despite the usefulness of BMI in the classification of subjects, [49] other variables like fat mass, fat-free mass, bone mineral density, and bone mineral content enable a more comprehensive analysis of anthropometry. Future studies on these topics needs to consider the complexity effects of celiac disease in anthropometric parameters to provide for an appropriate selection of assessment methods.…”

Kynurenine and Tetrahydrobiopterin Pathways Crosstalk in Pain Hypersensitivity

“…BH4 is also mandatory for the cleavage of ether lipids as well as the biosynthesis of nitric oxide ( Thöny et al, 2000 ; Werner et al, 2011 ). Recently, our group has uncovered other fundamental physiological roles for basal BH4 levels, as having antioxidant and anti-inflammatory properties, and being a mitochondrial activator as well as a memory enhancer ( Ghisoni et al, 2015a , b , 2016 ; De Paula Martins et al, 2018 ; Latini et al, 2018 ). We also described that exacerbated production of BH4 is pathogenic, causing pain, increasing the aggressiveness of the immune system and the progression of the symptoms of chronic diseases, including, chronic pain, asthma, multiple sclerosis, ulcerative colitis, rheumatoid arthritis, and cognitive impairment ( Latremoliere et al, 2015 ; Cronin et al, 2018 ; Fujita et al, 2019 ).…”

“Special K” Drug on Adolescent Rats: Oxidative Damage and Neurobehavioral Impairments

“…After 24 hours (training session), animals were resubmitted to the secure platform of the apparatus, and immediately after stepping down on the grid, they received a 0.4 mA, 1.0 s scrambled foot shock. During test sessions (1.5 h after training session), animals were placed on the secure platform and the step-down latency (maximum 180 s) was used as measure of retention (short-term memory) [37].…”