Iron is a key nutrient for cognitive function. During periods of high academic demand, brain and cognitive activity increase, potentially affecting iron intake and reserves. The present study aimed to investigate the impact of iron levels on cognitive function in a university sample, considering the influence of gender. A cross-sectional study was conducted with 132 university students (18–29 years) from the University of Castilla-La Mancha (Spain). A dietary record was formed through a questionnaire to analyze iron consumption, and blood and anthropometric parameters were measured. The Wechsler Adult Intelligence Scale-IV was used to determine the Intelligence Quotient (IQ), as well as the Verbal Comprehension Index (VCI), Working Memory Index (WMI), Processing Speed Index (PSI), and Perceptual Reasoning Index (PRI), to assess cognitive abilities. Among women, the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) was 21% and 4.2%, respectively. No ID or IDA was found in men. The impact of iron intake on IQ and cognitive abilities was mainly associated with the female population, where a positive association between iron intake, serum ferritin, and total IQ was revealed. In conclusion, low iron intake is related to poorer intellectual ability, suggesting that an iron-rich diet is necessary to maintain the academic level of university students.

Adenosine is a neuromodulator that has been involved in aging and neurodegenerative diseases as Alzheimer’s disease (AD). In the present work, we analyzed the possible modulation of purine metabolites, 5’nucleotidase (5′NT) and adenosine deaminase (ADA) activities, and adenosine monophosphate (AMP)-activated protein kinase (AMPK) and its phosphorylated form during aging in the cerebral cortex. Three murine models were used: senescence-accelerated mouse-resistant 1 (SAMR1, normal senescence), senescence-accelerated mouse-prone 8 (SAMP8, a model of AD), and the wild-type C57BL/6J (model of aging) mice strains. Glutamate and excitatory amino acid transporter 2 (EAAT2) levels were also measured in these animals. HPLC, Western blotting, and enzymatic activity evaluation were performed to this aim. 5′-Nucleotidase (5′NT) activity was decreased at six months and recovered at 12 months in SAMP8 while opposite effects were observed in SAMR1 at the same age, and no changes in C57BL/6J mice. ADA activity significantly decreased from 3 to 12 months in the SAMR1 mice strain, while a significant decrease from 6 to 12 months was observed in the SAMP8 mice strain. Regarding purine metabolites, xanthine and guanosine levels were increased at six months in SAMR1 without significant differences in SAMP8 mice. In C57BL/6J mice, inosine and xanthine were increased, while adenosine decreased, from 4 to 24 months. The AMPK level was decreased at six months in SAMP8 without significant changes nor in SAMR1 or C57BL/6J strains. Glutamate and EAAT2 levels were also modulated during aging. Our data show a different modulation of adenosine metabolism participants in the cerebral cortex of these animal models. Interestingly, the main differences between SAMR1 and SAMP8 mice were found at six months of age, SAMP8 being the most affected strain. As SAMP8 is an AD model, results suggest that adenosinergic metabolism is involved in the neurodegeneration of AD.

Cholesterol metabolism seems dysregulated and linked to amyloid-β (Aβ) formation in neurodegeneration, but the underlying mechanisms are poorly known. Resveratrol (RSV) is a polyphenol with antioxidant activity and neuroprotective properties. Here, we analyzed the effect of age and RSV supplementation on cholesterol metabolism in the brain and blood serum, and its potential link to Aβ processing, in SAMP8 mice—an animal model of aging and Alzheimer’s disease. In the brain, our results revealed an age-related increase in ApoE and unesterified cholesterol in the plasma membrane whereas LDL receptor, HMG-CoA reductase, HMG-CoA-C1 synthase, and ABCA1 transporter remained unaltered. Furthermore, BACE-1 and APP gene expression was decreased. This dysregulation could be involved in the amyloidogenic processing pathway of APP towards Aβ formation. In turn, RSV exhibited an age-dependent effect. While levels of unesterified cholesterol in the plasma membrane were not affected by RSV, several participants in cholesterol uptake, release, and de novo synthesis differed, depending on age. Thus, RSV supplementation exhibited a different neuroprotective effect acting on Aβ processing or cholesterol metabolism in the brain at earlier or later ages, respectively. In blood serum, HDL lipoprotein and free cholesterol were increased by age, whereas VLDL and LDL lipoproteins remained unaltered. Again, the protective effect of RSV by decreasing the LDL or increasing the HDL levels also seems to depend on the intervention’s moment. In conclusion, age is a prominent factor for cholesterol metabolism dysregulation in the brain of SAMP8 mice and influences the protective effects of RSV through cholesterol metabolism and Aβ processing.

Adenosine (ARs) and metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors (GPCRs) that are modulated in the brain of SAMP8 mice, an animal model of Alzheimer’s disease (AD). In the present work, it is shown the presence of ARs and mGluRs in blood serum and derived exosomes from SAMP8 mice as well as its possible modulation by aging and resveratrol (RSV) consumption. In blood serum, adenosine A₁ and A_2A receptors remained unaltered from 5 to 7 months of age. However, an age-related decrease in adenosine level was observed, while 5′-Nucleotidase activity was not modulated. Regarding the glutamatergic system, it was observed a decrease in mGluR₅ density and glutamate levels in older mice. In addition, dietary RSV supplementation caused an age-dependent modulation in both adenosinergic and glutamatergic systems. These GPCRs were also found in blood serum-derived exosomes, which might suggest that these receptors could be released into circulation via exosomes. Interestingly, changes elicited by age and RSV supplementation on mGluR₅ density, and adenosine and glutamate levels were similar to that detected in whole-brain. Therefore, we might suggest that the quantification of these receptors, and their corresponding endogenous ligands, in blood serum could have predictive value for early diagnosis in combination with other distinctive hallmarks of AD.

Numerous diseases, including obesity, diabetes, cardiovascular disorders, dementia-associated cognitive decline and sarcopenia are characterized by underlying inflammatory processes that contribute to disease progression. Purinergic signalling is widely recognized as a key modulator of inflammation. This system involves extracellular nucleotides (i.e., ATP, ADP, UTP, and UDP) and nucleosides (i.e., adenosine), which are detected by two receptor families: P2 receptors (for nucleotides) and P1 receptors (for nucleosides), expressed on various cell types. The regulation of extracellular ATP and adenosine levels is mediated by ecto-enzymes, particularly NTPDase1/CD39 and 5’-Nucleotidase/CD73, which sequentially degrade ATP to adenosine, as well as by nucleotide/nucleoside transporters. Generally, ATP-activated P2 receptors promote pro-inflammatory responses, whereas adenosine, acting via P1 receptors, exerts predominantly anti-inflammatory and immunosuppressive effects. Consequently, modulating inflammatory conditions through purinergic signalling may represent a promising therapeutic strategy for these diseases.In this research topic we have compiled 6 original research articles that provide up-to-date insights into the role of purinergic signalling in inflammatory diseases.Purinergic signalling in metabolic disordersMetabolic disorders represent a major cause of morbidity and mortality in developed countries. These disorders are often associated to obesity that is closely linked to chronic low-grade inflammation, primarily originating from dysfunctional adipose tissue. As adipose tissue expands, adipocytes become hypertrophic, leading to mechanical and metabolic stress that promotes the release of inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1apha (IL-1α) and monocyte chemoattractant protein-1 (MCP-1)These signals attract immune cells, particularly macrophages, that infiltrate the adipose tissue and shift toward a pro-inflammatory M1 phenotype [1]. The immune activation further amplifies inflammation through secretion of additional cytokines, production of reactive oxygen species (ROS), and activation of transcription factors like NF-κB. The inflammatory milieu disrupts insulin signalling pathways, contributing to insulin resistance and metabolic syndrome, thereby linking inflammation in obesity to a broad range of systemic dysfunctions [2].The low-grade inflammation that accompanies obesity very likely implies the activation of P2X7R, a main receptor for extracellular ATP (eATP) [3], contributing to adipose tissue dysfunction. Among the regulatory mechanisms of P2X7R expression, the role of sex steroids remains unclear. Authors described that under non-inflammatory (basal) conditions, treatment of human adipocytes with either testosterone (T) or 17β-estradiol (E2) did not significantly alter the P2X7R gene expression [4]. In contrast, exposure to dihydrotestosterone (DHT), a non-aromatizable androgen, led to a notable downregulation of P2X7R gene expression. Exposure of adipocytes to LPS, significantly increased P2X7R expression compared to baseline levels. Remarkably, pre-treatment with DHT prior to LPS exposure further enhanced the P2X7R gene expression, indicating that DHT sensitizes adipocytes to inflammatory activation. A similar enhancement was observed when adipocytes were pre-treated with testosterone in combination with anastrozole, an aromatase inhibitor that prevents conversion of testosterone into estradiol. While this combination had no significant effect on P2X7R expression at rest, it led to a pronounced upregulation following LPS stimulation. These findings highlight the modulatory role of sex steroids, particularly non-aromatizable androgens like DHT, on purinergic signaling in adipocytes. The results suggest that androgens can exert dual effects depending on the inflammatory state of the tissue and point to a sex-dependent regulation of adipose tissue inflammation via the P2X7R, a key component of the immune response machinery.Obesity can contribute to inflammatory evolution in different tissues and organs. Supernatants from the periprostatic adipose tissue (PPAT) of obese mice showed significantly elevated levels of total nitrate and nitrite (NOx⁻) and adenosine compared to controls, and diminished phenylephrine (PE)-induced contractions, but only in prostate tissues from obese mice [5]. This anticontractile effect was mitigated when the PPAT was co-incubated with NO pathway inhibitors or adenosine receptor (AR) antagonists, suggesting these pathways as mediators of the observed effects. PPAT supernatants from obese animals also enhanced the viability of PNT1-A normal human epithelial cells and suppressed caspase-3 expression, indicating anti-apoptotic activity. Moreover, BPH-1 (hyperplasic human epithelial) cells exhibited increased proliferation at all time points when exposed to PPAT supernatant, an effect significantly blunted by blocking NO signaling or AR activation. These findings highlight a functional role for NO and adenosine released from PPAT in modulating prostate contractility and epithelial cell proliferation. In obesity, this paracrine interaction may contribute to prostate dysfunction and disease progression. Further studies are warranted to explore the therapeutic potential of targeting PPAT-derived NO and adenosine in prostate-related pathologies.An established model for obesity-induced type 2 diabetes, represented by Zucker Diabetic Fatty (ZDF) rats was employed to investigate the impact of Cannabidiol (CBD), a nonpsychoactive compound derived from the cannabis plant with a wide range of reported therapeutic properties, on the adenosinergic signalling pathway within the myocardium, specifically focused on the left atria [6]. The animals, fed with a diabetogenic diet, received daily oral administration of CBD (60 mg/kg) or vehicle for four weeks. The...