RESUMO
The effects of neuroinvasion by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) become clinically relevant due to the numerous neurological symptoms observed in Corona Virus Disease 2019 (COVID-19) patients during infection and post-COVID syndrome or long COVID. This study reports the biofabrication of a 3D bioprinted neural-like tissue as a proof-of-concept platform for a more representative study of SARS-CoV-2 brain infection. Bioink is optimized regarding its biophysical properties and is mixed with murine neural cells to construct a 3D model of COVID-19 infection. Aiming to increase the specificity to murine cells, SARS-CoV-2 is mouse-adapted (MA-SARS-CoV-2) in vitro, in a protocol first reported here. MA-SARS-CoV-2 reveals mutations located at the Orf1a and Orf3a domains and is evolutionarily closer to the original Wuhan SARS-CoV-2 strain than SARS-CoV-2 used for adaptation. Remarkably, MA-SARS-CoV-2 shows high specificity to murine cells, which present distinct responses when cultured in 2D and 3D systems, regarding cell morphology, neuroinflammation, and virus titration. MA-SARS-CoV-2 represents a valuable tool in studies using animal models, and the 3D neural-like tissue serves as a powerful in vitro platform for modeling brain infection, contributing to the development of antivirals and new treatments for COVID-19.
Assuntos
COVID-19 , SARS-CoV-2 , Animais , Encéfalo , COVID-19/complicações , Humanos , Camundongos , Neurônios , Síndrome de COVID-19 Pós-AgudaRESUMO
Acute phenylalanine and tyrosine depletion (APTD) studies have been used to assess the role of the cathecholaminergic system in various aspects of human behaviour. In this study we conducted a randomized, double-blind, controlled and cross-over comparison to evaluate the effects of APTD on memory, attention and mood in normal subjects. Twelve healthy male volunteers were included in this study. The subjects ingested a nutritionally balanced mixture (B) or a similar mixture deficient in phenylalanine and tyrosine (PT-). Before and 5 h after ingestion of the drink, volunteers underwent tests on mood, memory and attention. Results of the memory tests showed that PT- mixture impaired word recall as measured in Rey's test (p = 0.016). The assessment of changes in mood showed that the balanced mixture improved scores of as alertness (VAMS factor I, p = 0.037) and the PT- mixture induces an opposite effect, increased scores of anxiety (Profiles of Mental State composed-anxious dimension, p = 0.022). These results suggest that tyrosine plasma levels and cathecholamines may be important factors in regulating mood and memory.