Attention Deficit Hyperactivity Disorder (ADHD) is a highly prevalent and disabling disorder that frequently persists into adulthood. Many patients are considered nonresponders to typical pharmacological treatments due to insufficient symptoms' reduction or the inability to tolerate the side effects of these medications. Agmatine is an endogenous neuromodulator with emotional- and cognitive-enhancing properties that arises as a promising agent to manage several Central Nervous System disorders. Here, we investigated the effects of chronic treatment with agmatine on behavioral impairments exhibited by adult Spontaneously Hypertensive Rats (SHR), an animal model for the study of ADHD. Adult male Wistar and SHR (3-4 months old) received intraperitoneal (i.p.) treatment with saline (NaCl 0.9%) or agmatine (30 mg/kg/day) during 20 consecutive days and were evaluated in a battery of behavioral tasks. Agmatine treatment improved olfactory and recognition memory impairments of SHR evaluated in the olfactory discrimination, object recognition, and social recognition memory tasks. In addition, agmatine administration improved the cognitive flexibility in the water maze test. Agmatine did not alter SHR's locomotor activity and hedonic-like behaviors observed in the open-field and splash tests, respectively. No changes were observed in SHR's systolic blood pressure following agmatine treatment. This study provides the first evidence that agmatine improves olfactory and cognitive impairments observed in an animal model of ADHD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Studies have revealed the dependence of glioma cells on iron, making them sensitive to ferroptosis. Ferroptosis can be triggered by inhibition of the xc- system, resulting in redox imbalance and membrane lipid peroxidation. The xc- system is composed of two coupled proteins, xCT and CD98hc. The control of transporters, such as xCT, by the CD98hc glycoprotein suggests that molecules targeting glycans may have an impact on the treatment of glioma. This study evaluated the effect of the Canavalia brasiliensis (ConBr) lectin on C6 glioma cells and compared it with erastin, an xc- system inhibitor. Both induced dose-dependent cell death, accompanied by an increase in the production of reactive oxygen species and a decrease in reduced glutathione. However, co-treatment did not show an additive effect. The analysis was updated by molecular dynamics assessments of the xc- system interacting with ConBr or erastin. The interaction of erastin with the xc- system affects its interaction with ConBr, reducing the antagonistic effect when both are in the protein complex. The data show that ConBr is effective in inducing cell death in glioma cells and regulates the xc system through interaction with CD98hc glycans, showing that lectins have the potential to promote ferroptosis in glioma cells.