Herpes Simplex Virus Type 1 Enhances Expression of the Synaptic Protein Arc for Its Own Benefit.

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus able to reach the central nervous system (CNS) after primary infection in oronasal mucosa. HSV-1 establishes latency inside neurons due the repression of its gene expression process, which is related to periodic reactivations in response to cellular stress conditions, constituting a risk factor for neurodegenerative diseases such as Alzheimer's disease (AD). The immediate-early gene Arc plays an essential role in neuronal morphology, synaptic plasticity and memory formation. Arc acts as a hub protein, interacting with components of the endocytic machinery required for AMPA receptor (AMPAR) recycling as well as with proteins of the post-synaptic density and actin cytoskeleton. However, to date, no studies have evaluated whether persistent neurotropic HSV-1 infection modulates the expression or function of Arc protein in brain tissue. Here, we report that neuronal in vivo and in vitro infection of HSV-1 significantly increases Arc protein levels, showing a robust perinuclear distribution in neuronal cell lines, a process that is dependent on an active HSV-1 replication cycle. Finally, we found that silencing Arc protein caused a decrease in HSV-1 proteins and viral progeny, suggesting that Arc is involved in the lifecycle of HSV-1. Our studies strongly suggest that pathogenicity of HSV-1 neuronal reactivations in humans could be mediated in part by Arc neuronal upregulation and its potential role in endocytic trafficking and AMPA-neuronal function impairment. Further studies are necessary to define whether this phenomenon could have repercussions in cognition and learning processes in infected individuals.

The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats.

OBJECTIVE: Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance. MATERIALS AND METHODS: Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups. RESULTS: Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin, in patients.

Effect of chronic administration of forskolin on glycemia and oxidative stress in rats with and without experimental diabetes.

Forskolin is a diterpene derived from the plant Coleus forskohlii. Forskolin activates adenylate cyclase, which increases intracellular cAMP levels. The antioxidant and antiinflammatory action of forskolin is due to inhibition of macrophage activation with a subsequent reduction in thromboxane B2 and superoxide levels. These characteristics have made forskolin an effective medication for heart disease, hypertension, diabetes, and asthma. Here, we evaluated the effects of chronic forskolin administration on blood glucose and oxidative stress in 19 male Wistar rats with streptozotocin-induced diabetes compared to 8 healthy male Wistar rats. Rats were treated with forskolin, delivered daily for 8 weeks. Glucose was assessed by measuring fasting blood glucose in diabetic rats and with an oral glucose tolerance test (OGTT) in healthy rats. Oxidative stress was assessed by measuring 8-hydroxydeoxyguanosine (8­OHdG) in 24-h urine samples. In diabetic rats, without forskolin, fasting blood glucose was significantly higher at the end than at the beginning of the experiment (8 weeks). In both healthy and diabetic rats, forskolin treatment lowered the fasting glucose at the end of the experiment but no effect was found on oral glucose tolerance. The 8-OHdG levels tended to be less elevated in forskolin-treated than in untreated group. Our results showed that chronic administration of forskolin decreased fasting blood glucose levels; however, the reductions of 8-OHdG were not statistically significant.