We investigated possible interaction between an arbovirus infection and the ME7 induced mice prion disease. C57BL/6, females, 6-week-old, were submitted to a bilateral intrahippocampal injection of ME7 prion strain (ME7) or normal brain homogenate (NBH). After injections, animals were organized into two groups: NBH (n = 26) and ME7 (n = 29). At 15th week after injections (wpi), animals were challenged intranasally with a suspension of Piry arbovirus 0.001% or with NBH. Behavioral changes in ME7 animals appeared in burrowing activity at 14 wpi. Hyperactivity on open field test, errors on rod bridge, and time reduction in inverted screen were detected at 15th, 19th, and 20th wpi respectively. Burrowing was more sensitive to earlier hippocampus dysfunction. However, Piry-infection did not significantly affect the already ongoing burrowing decline in the ME7-treated mice. After behavioral tests, brains were processed for IBA1, protease-resistant form of PrP, and Piry virus antigens. Although virus infection in isolation did not change the number of microglia in CA1, virus infection in prion diseased mice (at 17th wpi) induced changes in number and morphology of microglia in a laminar-dependent way. We suggest that virus infection exacerbates microglial inflammatory response to a greater degree in prion-infected mice, and this is not necessarily correlated with hippocampal-dependent behavioral deficits.

Background: Leptin is an essential hormone in the control of energy homeostasis, whose production and action may be altered in patients with lipodystrophy. Leptin synthesis occurs mainly in adipose tissue, therefore it depends on the amount of body fat. This study aimed to assess the abdominal fat of patients with HIV-associated lipodystrophy and its relationship with leptin levels. Methods: Analytical cross-sectional study involving 40 male patients with HIV-associated lipodystrophy. Serum levels of leptin were measured by ELISA, and insulin levels were measured by a chemiluminescence assay. HOMA-IR was used to evaluate insulin resistance: fasting serum insulin (μIU/mL) × (fasting plasma glucose (mmol/L)/22.5). Total body fat was estimated by skinfold measurements and bioimpedance. Patients with mixed lipodystrophy underwent abdominal CT for subcutaneous and visceral fat measurements, and the visceral-to-subcutaneous fat ratio (VSR) was calculated. Spearman correlation was applied for quantitative associations. Measures of central tendency were compared by the t-test or Mann-Whitney test, and analyses of variance were performed by Kruskal-Wallis test. Results: Forty patients, aged between 35 and 74 years, were evaluated: 27 with mixed lipodystrophy, 10 with lipoatrophy, and 3 with lipohypertrophy. Leptin levels correlated significantly with body fat percentage, BMI, and waist circumference, but not with age. Median levels of leptin were lower in patients with lipoatrophy compared to patients with mixed lipodystrophy (p=0.0393). According to CT results, 70,4% of the patients were classified as VSR>1, and 29,6% as VSR≤1. Significant correlations were found between leptin and visceral fat (CT), insulin, and HOMA-IR, but not between leptin and subcutaneous fat (CT). Conclusions: Our preliminary results suggest that body fat, especially the visceral component, remains the central determinant of leptin levels in patients with mixed lipodystrophy. Also, higher levels of leptin seem to be related to insulin resistance in patients with HIV-associated lipodystrophy, regardless of clinical form.