5-Lipoxygenase is a key determinant of acute myocardial inflammation and mortality during Trypanosoma cruzi infection

This study provides evidence supporting the idea that although inflammatory cells migration to the cardiac tissue is necessary to control the growth of Trypanosoma cruzi, the excessive influx of such cells during acute myocarditis may be deleterious to the host. Production of lipid mediators of inflammation like leukotrienes (LTs) along with cytokines and chemokines largely influences the severity of inflammatory injury in response to tissue parasitism. T. cruzi infection in mice deficient in 5-lipoxygenase (5-LO), the enzyme responsible for the synthesis of LTs and other lipid inflammatory mediators, resulted in transiently increased parasitemia, and improved survival rate compared with WT mice. Myocardia from 5-LO^?/? mice exhibited reduced inflammation, collagen deposition, and migration of CD4⁺, CD8⁺, and IFN-γ-producer cells compared with WT littermates. Moreover, decreased amounts of TNF-α, IFN-γ, and nitric oxide synthase were found in the hearts of 5-LO^?/? mice. Interestingly, despite of early higher parasitic load, 5-LO^?/? mice survived, and controlled T. cruzi infection. These results show that efficient parasite clearance is possible in a context of moderate inflammatory response, as occurred in 5-LO^?/? mice, in which reduced myocarditis protects the animals during T. cruzi infection.     

Prenatal Stress Impairs Spinal Cord Oligodendrocyte Maturation via BDNF Signaling in the Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis

One of the most substantial and established environmental risk factors for neurological and psychiatric disorders is stress exposure, whose detrimental consequences hinge on several variables including time. In this regard the gestational period is known to present an intrinsic vulnerability to environmental insults and thus stressful events during pregnancy can lead to severe consequences on the offspring’s brain development with long-term repercussions throughout adulthood. On this basis, we investigated the long-lasting impact of prenatal stress exposure on the susceptibility to the experimental autoimmune encephalomyelitis (EAE), a well-established murine model of multiple sclerosis. Although stress is considered a triggering factor for this chronic, progressive, autoimmune disease, little is known about the underlying mechanisms. To this end, EAE was induced by immunization with MOG35-55/CFA and pertussis toxin administration in adult female C57BL/6 mice born from control or stressed dams exposed to restraint stress during the last days of gestation. Our results demonstrate that gestational stress induces a marked increase in the severity of EAE symptoms in adulthood. Further, we highlight an altered maturation of oligodendrocytes in the spinal cord of prenatally stressed EAE mice, as indicated by the higher levels of GPR17, a marker of immature oligodendrocyte precursor cells. These behavioral and molecular alterations are paralleled by changes in the expression and signaling of the neurotrophin BDNF, an important mediator of neural plasticity that may contribute to stress-induced impaired remyelination. Since several already marketed drugs are able to modulate BDNF levels, these results pave the way to the possibility of repositioning these drugs in multiple sclerosis.

     

Annual oscillation of preferred temperature in the freshwater snail Lymnaea auricularia: effect of light and temperature

The thermal preference of the freshwater snail Lymnaea auriculria (Gastropoda: Pulmonata), measured 49 times over 3 years, oscillated around a mean of 19·3°C, with an amplitude of 13·4°C. This oscillation was significantly phase-linked to both the natural photoperiod and natural ambient temperature. Lymnaea hatched and maintained in constant conditions of temperature (21°C) and photoperiod (12 h) over 2 years showed a constant thermal preference of 19·8±1·4°C. The preference was maintained between 19·5 and 20·4°C when the snails were kept at 5, 15, 20 and 27°C and in photoperiods of 8 and 16 h. In a changing artificial photoperiod which followed an annual cycle, the preference fluctuated about a mean of 19·3°C with an amplitude of 3·9°C. When the photoperiod was constant but the temperature oscillated the preference remained constant. Thus the circannual cycle seems to be an exogenous oscillation entrained by the photoperiod.