Neuroprotective effect of long-term resistance physical exercise against memory damage elicited by a lipopolysaccharide-induced neuroinflammation model in male rats.

Resistance exercise training (RET) is considered an excellent tool for preventing diseases with an inflammatory background. Its neuroprotective, antioxidant, and anti-inflammatory properties are responsible for positively modulating cholinergic and oxidative systems, promoting neurogenesis, and improving memory. However, the mechanisms behind these actions are largely unknown. In order to investigate the pathways related to these effects of exercise, we conducted a 12-week long-term exercise training protocol and used lipopolysaccharide (LPS) to induce damage to the cortex and hippocampus of male Wistar rats. The cholinergic system, oxidative stress, and histochemical parameters were analyzed in the cerebral cortex and hippocampus, and memory tests were also performed. It was observed that LPS: (1) caused memory loss in the novel object recognition (NOR) test; (2) increased the activity of acetylcholinesterase (AChE) and Iba1 protein density; (3) reduced the protein density of brain-derived neurotrophic factor (BDNF) and muscarinic acetylcholine receptor M1 (CHRM1); (4) elevated the levels of lipid peroxidation (TBARS) and reactive species (RS); and (5) caused inflammatory damage to the dentate gyrus. RET, on the other hand, was able to prevent all alterations induced by LPS, as well as increase per se the protein density of the alpha-7 nicotinic acetylcholine receptor (nAChRα7) and Nestin, and the levels of protein thiols (T-SH). Overall, our study elucidates some mechanisms that support resistance physical exercise as a valuable approach against LPS-induced neuroinflammation and memory loss.

Resistance physical exercise alleviates lipopolysaccharide-triggered neuroinflammation in cortex and hippocampus of rats via purinergic signaling.

Resistance physical exercise has neuroprotective and anti-inflammatory effects on many known diseases and, therefore, it has been increasingly explored. The way in which this type of exercise exerts these actions is still under investigation. In this study, we aimed to analyze the enzymes and components of the purinergic system involved in the inflammatory process triggered by the P2X7R. Rats were divided into four groups: control, exercise (EX), lipopolysaccharide (LPS), and EX + LPS. The animals in the exercise groups were subjected to a 12-week ladder-climbing resistance physical exercise and received LPS after the last session for sepsis induction. Enzymes activities (NTPDase, 5'-nucleotidase, and adenosine deaminase), purinoceptors' density (P2X7R, A1, and A2A), and the levels of inflammatory indicators (pyrin domain-containing protein 3 (NLRP3), Caspase-1, interleukin (IL)- 6, IL-1B, and tumor necrosis factor (TNF) -α) were measured in the cortex and hippocampus of the animals. The results show that exercise prevented (in the both structures) the increase of: 1) nucleoside-triphosphatase (NTPDase) and 5'-nucleotidase activities; 2) P2X7R density; 3) NLRP3 and Caspase-1; and 4) IL-6, IL-1ß, and TNF-α It is suggested that the purinergic system and the inflammatory pathway of P2X7R are of fundamental importance and influence the effects of resistance physical exercise on LPS-induced inflammation. Thus, the modulation of the P2X7R by resistance physical exercise offers new avenues for the management of inflammatory-related illnesses.

Diabetes and hypertension: Pivotal involvement of purinergic signaling.

Diabetes mellitus (DM) and hypertension are highly prevalent worldwide health problems and frequently associated with severe clinical complications, such as diabetic cardiomyopathy, nephropathy, retinopathy, neuropathy, stroke, and cardiac arrhythmia, among others. Despite all existing research results and reasonable speculations, knowledge about the role of purinergic system in individuals with DM and hypertension remains restricted. Purinergic signaling accounts for a complex network of receptors and extracellular enzymes responsible for the recognition and degradation of extracellular nucleotides and adenosine. The main components of this system that will be presented in this review are: P1 and P2 receptors and the enzymatic cascade composed by CD39 (NTPDase; with ATP and ADP as a substrate), CD73 (5'-nucleotidase; with AMP as a substrate), and adenosine deaminase (ADA; with adenosine as a substrate). The purinergic system has recently emerged as a central player in several physiopathological conditions, particularly those linked to inflammatory responses such as diabetes and hypertension. Therefore, the present review focuses on changes in both purinergic P1 and P2 receptor expression as well as the activities of CD39, CD73, and ADA in diabetes and hypertension conditions. It can be postulated that the manipulation of the purinergic axis at different levels can prevent or exacerbate the insurgency and evolution of diabetes and hypertension working as a compensatory mechanism.

Epidemiological study of paracoccidioidomycosis and histoplasmosis in a suburb of San Félix city, Bolívar state, Venezuela.

Epidemiologic studies of deep mycosis have been scarce in Bolivar state, where paracoccidioidomycosis and histoplasmosis are considered as endemic diseases. The aim of this study was to determine paracoccidioidomycosis and histoplasmosis prevalences in people from a suburb of San Féix, Bolívar state, Venezuela. Three-hundred volunteers agreed to participate in this study and they were inoculated with paracoccidioidine and histoplasmine. Identification and epidemiologic data were registered. Reading of skin tests after 24 hours was performed in 275 persons. Paracoccidioidine test was positive in 10.2% (n=28). A higher percentage of positive reactions in the age group of 40-50 years old (n=10; 35.7%) was observed. Bricklayers, farmers and miners were positive in 27.3% (3 out of 11), a higher percentage than in people with other occupations. Histoplasmine test was positive in 7.6% of cases (n=21). The higher percentage of reactivity was observed in the age group of 40-50 years old (n=9; 42.9%). There was a direct proportional relationship between staying time in the locality and H. capsulatum infection mainly in persons staying in the area for more than 30 years (p < 0.05). These results showed low prevalences of P. brasiliensis and H. capsulatum infection in this area.

Epidemiological study of paracoccidioidomycosis and histoplasmosis in a suburb of San Félix city Bolívar state Venezuela

Epidemiologic studies of deep mycosis have been scarce in Bolívar state, where paracoccidioidomycosis and histoplasmosis are considered as endemic diseases. The aim of this study was to determine paracoccidioidomycosis and histoplasmosis prevalences in people from a suburb of San Félix, Bolívar state, Venezuela. Three-hundred volunteers agreed to participate in this study and they were inoculated with paracoccidioidine and histoplasmine. Identification and epidemiologic data were registered. Reading of skin tests after 24 hours was performed in 275 persons. Paracoccidioidine test was positive in 10.2% (n=28). A higher percentage of positive reactions in the age group of 40-50 years old (n=10; 35.7%) was observed. Bricklayers, farmers and miners were positive in 27.3% (3 out of 11), a higher percentage than in people with other occupations. Histoplasmine test was positive in 7.6 percent of cases (n= 21). The higher percentage of reactivity was observed in the age group of 40-50 years old (n=9; 42.9%). There was a direct proportional relationship between staying time in the locality and H. capsulatum infection mainly in persons staying in the area for more than 30 years (p<0.05). These results showed low prevalences of P. brasiliensis and H. capsulatum infection in this area.

El estudio epidemiológico de las micosis profundas ha sido escaso en el estado Bolívar donde la paracoccidioidomicosis e histoplasmosis son endémicas. El objetivo de este estudio fue determinar la prevalencia de infecciones por Paracoccidioides brasiliensis e Histoplasma capsulatum en individuos residenciados en una población suburbana de San Félix, estado Bolívar, Venezuela. Se administró paracoccidioidina e histoplasmina a 300 personas voluntarias. Se realizó lectura de las pruebas a las 24 horas. La paracoccidioidina fue positiva en el 10,2% (n=28). Se observó mayor porcentaje de positividad en el grupo de 40-50 años (n=10; 35,7%). Las ocupaciones de riesgo: albañiles, agricultores y mineros, presentaron un porcentaje de positividad de 27,3% (3 de 11), mayor que el de los individuos sin riesgo aparente: mecánicos, oficios del hogar y estudiantes (25 de 264; 9,5 %) (p=0,04). La histoplasmina fue positiva en el 7,6% (n=21). El mayor porcentaje de intradermorreacción positiva se observó entre los 40-50 años (n=9; 42,9%). Hubo relación significativa entre el tiempo de residencia en la localidad y la infección por H. capsulatum, demostrándose en los individuos con más de 30 años en esa localidad (p<0,05). Estos resultados muestran una prevalencia relativamente baja de infecciones por P. brasiliensis y de H. capsulatum en el área estudiada.