ABSTRACT
Zika virus (ZIKV) infection during pregnancy is associated with a spectrum of developmental impairments known as congenital Zika syndrome (CZS). The prevalence of this syndrome varies across ZIKV endemic regions, suggesting that its occurrence could depend on cofactors. Here, we evaluate the relevance of protein malnutrition for the emergence of CZS. Epidemiological data from the ZIKV outbreak in the Americas suggest a relationship between undernutrition and cases of microcephaly. To experimentally examine this relationship, we use immunocompetent pregnant mice, which were subjected to protein malnutrition and infected with a Brazilian ZIKV strain. We found that the combination of protein restriction and ZIKV infection leads to severe alterations of placental structure and embryonic body growth, with offspring displaying a reduction in neurogenesis and postnatal brain size. RNA-seq analysis reveals gene expression deregulation required for brain development in infected low-protein progeny. These results suggest that maternal protein malnutrition increases susceptibility to CZS.
Subject(s)
Malnutrition/complications , Zika Virus Infection/congenital , Zika Virus Infection/complications , Animals , Animals, Newborn , Body Weight , Brain/enzymology , Brain/pathology , Brazil/epidemiology , Diet, Protein-Restricted , Disease Outbreaks , Embryo, Mammalian/pathology , Female , Gene Expression Regulation, Developmental , Malnutrition/virology , Mice, Inbred C57BL , Microcephaly/complications , Microcephaly/virology , Neurogenesis , Organ Size , Pregnancy , Syndrome , Viral Load , Zika Virus Infection/virologyABSTRACT
Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly.
Subject(s)
Neovascularization, Physiologic , Zika Virus Infection/congenital , Zika Virus/physiology , Animals , Blood Vessels/pathology , Brain/blood supply , Brain/pathology , Brain/virology , Disease Models, Animal , Embryo, Mammalian/pathology , Embryo, Mammalian/virology , Endothelial Cells/pathology , Endothelial Cells/virology , Female , Mice, Inbred C57BL , Neurogenesis , Organ Size , Zika Virus Infection/pathology , Zika Virus Infection/virologyABSTRACT
Although the toxic potential of tannery effluents (TE) is acknowledged, the impacts these residues have on mammals who intake water contaminated with this pollutant are not completely known. Thus, in order to broaden the knowledge about how these contaminants affect the biota, the aim of the current study is to assess different behavioral categories (e.g.: sexual odor preference, opposite-sex attraction, and sexual discrimination) related to the sexual motivation and pre-copulation of male Swiss mice subjected to TE intake for 30 days, at concentrations 0.8% and 22%. The animals were subjected to locomotor performance evaluation through the Basso Mouse Scale (BMS), as well as to the open field (OF), odor preference (OPT), sexual orientation (SOT) and to scent marking tests (SMT) one week before the experiment ended. Our results evidenced that the treatments did not affect the animals' locomotor activity (in OF and BMS) or caused changes compatible to anxiogenic or anxiolytic behavior (in OF). However, mice exposed to TE (at both concentrations) presented discriminatory capacity deficit in the OPT test at the time to distinguish conspecific odors from the same sex, and from the opposite sex. They randomly explored (without preference) males and females, did not responded to stimuli in the SOT test, as well as did not appear capable of detecting female odor (in estrus phase) during the SMT. Thus, the current study was pioneer in evidencing that TE can influence the reproduction and the population dynamics of small rodents who intake water contaminated with the pollutant.
Subject(s)
Industrial Waste/adverse effects , Sexual Behavior, Animal/drug effects , Smell/physiology , Water Pollutants, Chemical/pharmacology , Animals , Female , Locomotion/drug effects , Male , Mice , Odorants , Sexual Behavior/drug effects , TanningABSTRACT
Two cases of spontaneous epidural hematoma of the lumbar region are reported. Some considerations are drawn about the values of the early diagnosis before the incidence of neurological sequela. The clinical and radiological findings and the treatment of these hematomas are discussed. Lumbar puncture and myelography are the best method for the diagnosis. Treatment should be surgical, consisting of laminectomy with total excision of the hematoma.
