3D Bioprinted Neural-Like Tissue as a Platform to Study Neurotropism of Mouse-Adapted SARS-CoV-2.

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.

Behavioural effects of acute phenylalanine and tyrosine depletion in healthy male volunteers.

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.