The aim of this study was to investigate the effect of rosuvastatin treatment on memory impairment, and anxiogenic-like effects in mice chronically infected with Toxoplasma gondii. For this, Balb/c mice were infected orally with chronic ME-49 strain of Toxoplasma gondii. Oral treatment with rosuvastatin (40mg/kg/day) started on the 51st day post-infection and was performed daily for 21 days. After completion of treatment, anxiety-like effects and locomotion were investigated in the open field (OF) test, whereas novel object recognition (NOR) test was used for evaluation of short- and long-term memory. At the end of the experiments, the brain was collected for Toxoplasma gondii DNA quantification and histopathological analysis. Infection with ME-49 strain decreased the time spent in the center of OF, indicating an anxiogenic effect, without affecting total and peripheral locomotion. Rosuvastatin treatment inhibited the change in the center time. Besides, pharmacological treatment increased total and central locomotion in both non-infected and infected animals. Infection also impaired both short- and long-term memory in the NOR test, and these effects were reverted by rosuvastatin treatment. In addition to effects in behavioral changes, rosuvastatin also reduced parasite load in the brain and attenuated signs of brain inflammation such as perivascular cuffs, inflammatory cell infiltration and tissue damage. These findings indicate for the first time the efficacy of rosuvastatin in treatment of memory impairment and anxiogenic effect evoked by infection with Toxoplasma gondii. These effects might be mediated by reduced cyst load, which in turn decrease inflammation and damage in the brain.
The synthesis of estradiol by the granulosa cells is a prominent event in ovarian physiology and depends on the expression of P450 AROM . FSH induces the expression of P450 AROM in granulosa cells as a result of the presence in the ovarian promoter of a CRE (cAMP response element)-like sequence (CLS). In rodents, LH downregulates aromatase expression during luteinization by an as yet undescribed mechanism. In granulosa cells, LH increases the expression of the inducible cAMP early repressor (ICER), an isoform of CREM (cAMP-responsive element modulator) that represses cAMP-induced transcription. The possibility that ICER represses the activity of the aromatase ovarian promoter, thus being part of the mechanism underlying the effects of LH was investigated. We have found that: (1) nuclear proteins from forskolinstimulated granulosa cells were specifically bound to an oligonucleotide containing the CLS sequence of the CYP19 ovarian promoter and one out of the two protein-DNA complexes formed was supershifted by an anti-CREM antibody; (2) in granulosa cells, forskolin-induced increases in P450 AROM promoter luciferase reporter gene activity were prevented by the transient overexpression of ICER; (3) similar results were obtained in 8-Br-cAMPstimulated R2C cells, a Leydig tumor cell line routinely used for the study of P450 AROM promoter activity; (4) both ICER mRNA levels and P450 AROM promoterdriven luciferase activity were elevated 6 and 12 h after stimulation of R2C cells with 8-Br-cAMP and were decreased 24 and 48 h later; (5) in an R2C polyclonal line overexpressing ICER, the promoter activity at early stages of stimulation was completely attenuated, while 24 and 48 h downregulation was prevented in another R2C line stably transfected with an antisense ICER construct. These results suggest that ICER represses CYP19 ovarian promoter and that LH-induced expression of ICER may serve to downregulate P450 AROM transcription in granulosa cells during luteinization.
Medicinal plants are attractive sources in the search of bioactive compounds in the treatment of infectious diseases. Considering that the infectious agent often develops resistance to existing treatments rapidly, the searches for such compounds are a never-ending process. One such infection, caused by Candida spp. is candidiasis, which is a public health problem. Additionally, many strains have resistance to traditional therapies. Therefore, we tested the antifungal activity of four compounds present in Mentha spp. with promising antifungal precedents. We measured inhibition of growth by microdilution, disruption of biofilm viewed by electron microscopy, inhibition of germ tube formation by optical microscopy and toxicity on HaCaT cells. Tests showed that the compounds tested had antifungal activity with a minimum inhibitory concentration of 0.5 mg/mL, at least, 50% of biofilm inhibition in the 0.5 mg/mL concentration, an inhibition of polymorphism to 86% and the changes in the cell envelope of yeast (SEM) and cell viability above 50% among the Candida strains tested. Therefore, the compounds exhibit promising antifungal properties and provide a reasonable therapeutic window to be used in association with other traditional antimitotic.
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