Neurological complications affecting the central nervous system have been reported in adult patients infected by Zika virus (ZIKV) but the underlying mechanisms remain unknown. Here, we report that ZIKV replicates in human and mouse adult brain tissue, targeting mature neurons. ZIKV preferentially targets memory-related brain regions, inhibits hippocampal long-term potentiation and induces memory impairment in adult mice. TNF-α upregulation, microgliosis and upregulation of complement system proteins, C1q and C3, are induced by ZIKV infection. Microglia are found to engulf hippocampal presynaptic terminals during acute infection. Neutralization of TNF-α signaling, blockage of microglial activation or of C1q/C3 prevent synapse and memory impairment in ZIKV-infected mice. Results suggest that ZIKV induces synapse and memory dysfunction via aberrant activation of TNF-α, microglia and complement. Our findings establish a mechanism by which ZIKV affects the adult brain, and point to the need of evaluating cognitive deficits as a potential comorbidity in ZIKV-infected adults.
Arnica montana is a medicinal plant native to Europe and used topically to treat contusions, inflammations, and muscular aches. Studies have confirmed the anti-inflammatory activity of extracts of this plant, which can be attributed to the presence of lactones. Its use in Brazil has traditionally been substituted by the species Solidago chilensis, which demonstrates similar therapeutic activity but is more adapted to a tropical climate. It is known that S. chilensis can be used as a substitute for A. montana as they both contain similar active compounds. We acquired eight different commercial brands of "arnica" sold in Rio de Janeiro State, Brazil, in 2013. The analyses of these products were divided into four categories: labeling, macroscopic, microscopic, and microchemical analysis. Labeling analysis followed RDCs ("Resolução de Diretoria Colegiada") standards (10/2010 through 26/2014). The morphological analyses were performed using microscopic techniques and were followed by microchemical analyses. Our results indicated that none of the samples were in complete conformity with labeling standards, the material was poorly conserved, contaminants were abundantly present, the species were incorrectly identified, and the directions of use were inadequate and potentially dangerous to human health.
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