Melisa Carolina Monteleone

Long COVID is increasingly associated with persistent neurological and cognitive symptoms, yet its underlying mechanisms remain unclear. Vascular dysregulation, endothelial dysfunction, and microvascular injury have been proposed as potential contributors. Arterial spin labeling (ASL) MRI allows noninvasive quantification of cerebral blood flow (CBF) and assessment of vascular function. Previous studies have reported hypoperfusion in long COVID patients, but few have accounted for delayed arterial transit time, which can affect ASL quantification. The spatial coefficient of variation (sCOV) has been previously used as a proxy of arterial transit time, providing a noninvasive marker of global cerebrovascular function. We examined 186 adults from an Argentine cohort (145 long COVID and 41 controls), approximately 2 years postinfection. Three‐dimensional pulsed ASL data were processed with ExploreASL to quantify CBF and sCOV in gray matter and lobar regions. Group comparisons were performed using multivariate models adjusted for age, sex, and white matter hyperintensity (WMH) volume. Long COVID participants showed significantly higher global gray matter sCOV compared with controls ( p = 0.02), with consistent regional trends across the frontal (L: p = 0.05; R: p = 0.07), temporal (L: p = 0.05; R: p = 0.08), parietal (L: p = 0.07; R: p = 0.06), occipital (L: p = 0.08; R: p = 0.05), and insular (L: p = 0.01; R: p = 0.15) lobes after FDR correction. Mean global, lobar, and regional gray matter CBF and WMH volumes did not differ significantly between groups. Increased sCOV, reflecting delayed arterial transit and reduced vascular efficiency, indicates widespread cerebrovascular dysfunction in the absence of perfusion deficits and not associated with white matter hyperintensities. These findings provide evidence of global vascular impairment in long COVID and support sCOV as a sensitive, noninvasive biomarker of cerebrovascular health.

The Argentine Group for Extracellular Vesicles (GAVE) was established in 2022 with the objective of bringing together researchers working in Argentina dedicated to extracellular vesicle (EV) studies. Following its successful inaugural meeting in 2023, the II GAVE Workshop was held on 12-13 September 2024, at the University of Buenos Aires, Argentina. This event brought together over 140 participants from diverse disciplines, fostering collaboration and strengthening the national EV research field. Moreover, international speakers and renowned experts in their fields shared valuable insights and experiences with the audience. Despite the challenges posed by the national government's funding cuts, the 2024 GAVE workshop showcased the Argentine scientists' strong commitment to high-quality research and the growth of local science in the field of EVs. Supported by international organizations and local companies, the II GAVE Workshop prioritized inclusivity and provided valuable networking opportunities, particularly for students and early-career researchers. This financial support was fundamental to broadening the impact of the event by promoting the assistance of underrepresented groups. This Meeting Review highlights the outcomes of our workshop and shows the advances of the Argentinian scientific community involved in EV research.

Chronic stress can trigger several pathologies including mood disorders for which no clear diagnostic molecular markers have been established yet. Attractive biomarker sources are extracellular vesicles (EVs). Evs are released by cells in health and disease and contain genetic material, proteins and lipids characteristic of the cell state. Here we show that Evs recovered from the blood of animals exposed to a repeated interrupted stress protocol (RIS) have a different protein profile compared to those obtained from control animals. Proteomic analysis indicated that proteins differentially present in bulk serum Evs from stressed animals were implicated in metabolic and inflammatory pathways and several of them were previously related to psychiatric disorders. Interestingly, these serum Evs carry brain-enriched proteins including the stress-responsive neuronal protein M6a. Then, we used an in-utero electroporation strategy to selectively overexpress M6a-GFP in brain neurons and found that M6a-GFP could also be detected in bulk serum Evs suggesting a neuronal origin. Finally, to determine if these Evs could have functional consequences, we administered Evs from control and RIS animals intranasally to naïve mice. Animals receiving stress EVs showed changes in behavior and brain M6a levels similar to those observed in physically stressed animals. Such changes could therefore be attributed, or at least in part, to EV protein transfer. Altogether these findings show that EVs may participate in stress signaling and propose proteins carried by EVs as a valuable source of biomarkers for stress-induced diseases.

Prenatal stress (PS) is a major risk factor for the development of emotional disorders in adulthood that may be mediated by an altered hypothalamic–pituitary–adrenal axis response to stress. Although the early onset of stress-related disorders is recognized as a major public health problem, to date, there are relatively few studies that have examined the incidence of early-life stressors in younger individuals. In this study, we assessed PS impact on the stress-coping response of juvenile offspring in behavioral tests and in the induced molecular changes in the hippocampus. Furthermore, we assessed if pregnancy stress could be driving changes in patterns of maternal behavior during early lactation. We found that PS modified stress-coping abilities of both sex offspring. In the hippocampus, PS increased the expression of bdnf-IV and crfr1 and induced sex difference changes on glucocorticoids and BDNF mRNA receptor levels. PS changed the hippocampal epigenetic landscape mainly in male offspring. Stress during pregnancy enhanced pup-directed behavior of stressed dams. Our study indicates that exposure to PS, in addition to enhanced maternal behavior, induces dynamic neurobehavioral variations at juvenile ages of the offspring that should be considered adaptive or maladaptive, depending on the characteristics of the confronting environment. Our present results highlight the importance to further explore risk factors that appear early in life that will be important to allow timely prevention strategies to later vulnerability to stress-related disorders.