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Recently, the purine nucleoside inosine has been demonstrated to have several neuroprotective effects. Similarly, exercise training has well-known beneficial effects on mental health and cognitive function. Neuronal nitric oxide synthase (nNOS) is a key neuronal messenger in several brain regions, and the downregulation of nNOS has been shown to improve brain function. However, whether inosine and exercise training have combined effects on nNOS pathway-related proteins in the brain remains unknown. We found, for the first time, that inosine monophosphate (IMP), which is a precursor of inosine, decreases nNOS levels in the ventral hippocampus (vHp) and the cerebellum (Ce), but not in the dorsal hippocampus (dHp). In the vHp, the phosphorylation of cAMP response element-binding protein (CREB) was also upregulated, which negatively correlated with nNOS protein levels. In the cerebral cortex (Cx), no significant activation of the nNOS pathway was observed. In the dHp, vHp, Cx, and Ce, no interactions between the effects of IMP and exercise on nNOS protein and CREB phosphorylation levels were observed. The phosphorylation of nNOS was regulated by the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. Although IMP induced minor changes in Akt phosphorylation, nNOS phosphorylation was unchanged by either IMP or exercise. In conclusion, in the vHp, which is associated with emotional behavior, IMP decreased nNOS levels and activated CREB, suggesting that IMP can elicit anxiolytic effects.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new viral disease that has gained global attention owing to its ability to provoke community and health-care-associated outbreaks of severe infections in human populations. RG7440 The virus poses serious challenges to clinical management because there are still no approved anti- SARS-CoV-2 drugs available. In this mini-review, we summarize the much updated published reports that demonstrate the mechanism of SARS-CoV-2 entry into host cells, and discuss the availability and development of attractive host-based therapeutic options for SARS-CoV-2 infections.Dopamine (DA) in medial prefrontal cortex is crucial in extinction of aversive or appetitive experiences. Although attention has been mostly focused on the infralimbic area of prefrontal cortex, a role of the prelimbic (PL) area has been envisaged pointing to DA transmission in the extinction of drug conditioned behavior. Evidence shows that DA exerts its action also via both D1 and D2 receptor subtypes. Here we investigated the effects of D1 and D2 receptor agonist microinfusion in the PL cortex of C57BL/6J mice on expression and extinction of amphetamine-induced conditioned place preference (CPP), in order to ascertain the effects of selective vs concomitant receptor subtypes stimulation. SKF38393 and Quinpirole were used at doses not impairing expression of amphetamine-induced CPP on the day of infusion. Acute infusion of each agonist alone did not affect extinction in subsequent days in comparison with Vehicle-treated mice, while concomitant infusion of both agonists produced a clear-cut advance of extinction of preference for the compartment previously paired with amphetamine. These results show that concomitant stimulation of D1 and D2 receptors in PL is required to foster extinction suggesting a synergic action between receptors or a heteromeric receptor involvement.Objective The effects of aminoguanidine (AG) were investigated in a rat model of lipopolysaccharide (LPS)-induced anxiety- and depression-like behaviors. Materials and methods The animals were allocated to five groups (n = 10 in each) and treated by (1) saline as a control group, (2) LPS 1 mg/kg injected two hours before behavioral tests, (3-5) AG 50, 100 or 150 mg/kg before LPS. The open-field test (OFT), elevated plus maze test (EPT), and forced swimming (FS) tests were performed. The brains and blood were then collected to examine oxidative stress and inflammation criteria. Results LPS increased the immobility while decreased the active time in the FS test. In EPT, LPS decreased the time spent in the open arms, whereas it increased the time spent in the closed arms. In OFT, LPS decreased the time spent in the central zone compared with the controls. A higher dose of selenium improved the performances of the rats in behavioral tests. LPS injection also increased malondialdehyde (MDA) while it decreased thiol, superoxide dismutase (SOD), and catalase. LPS also increased interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), but decreased IL-10 in the LPS group. AG protected the brain from inflammation and oxidative damage. Conclusion It was demonstrated that AG improves the behaviors of depression and anxiety in a rat model of LPS-induced anxiety- and depression-like behaviors. Moreover, the effects of AG were accompanied by improved inflammation and oxidative damage biomarkers in brain tissues.The Prefrontal cortex (PFC) has been highly related to executive functions such as working memory (WM). This study assesses the activity of the PFC in performing the Sternberg WM task (ST) with three levels of difficulty (easy, medium and hard) using the near-infrared spectroscopy (fNIRS) technique. Participants were 43 young and healthy right-handed women. Nine WM task blocks were pseudo randomly presented, three for each difficulty task. The results showed that the participant's performance was better in the easy trials than in the medium and hard trials. Performance in the medium trials was also better than in the hard ones. Bonferroni-corrected paired post-hoc t-tests indicated higher oxygenation in medium and hard tasks than in the easy ones for times between 13 and 42 s in the left lateral PFC and in both, medial and lateral, right PFC. Significant differences in Oxygenated hemoglobin (HbO), Total hemoglobin (HbT) and oxygenation (Oxy) changes depending on the Sternberg WM task were found. Unlike previous studies with fNIRS and WM, the current study uses a highly controlled WM task that differentiates between encoding, retention and retrieval phases, comparing different levels of task load.
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