Publications

We have identified over 130,000 unique circRNAs in 6 mouse models of ASD. DECs per se are shared by a few animal models. However, functional analysis revealed that the DECs from distinct models share a similar profile of changes, mostly related to synaptic structure and function. Regarding translational alterations, around 2% of DECs in mice are orthologous to DECs in autistic individuals. We hope the broad identification of circRNAs can help researchers further explore their selected mouse models.

Subjective cognitive decline (SCD) is defined as a memory complaint in individuals without an objective measure of cognitive impairment. In this study, we investigated the morphometric and metabolic brain changes in individuals presenting with SCD. Compared to CU individuals, SCD subjects showed increased cortical thickness in the right hemisphere rostral middle frontal gyrus, while glucose metabolism was increased in the right medial temporal lobe, including the hippocampus, and right occipital cortex.

We developed a set of 15 heuristics to evaluate the usability of four circRNAs identification tools. Cosmetic and minor severity issues are present in all tools evaluated. Severe problems are less frequent but affect critical parts of the software. The use of heuristics could help promptly evaluate usability during the development cycle.

We analyzed microarray and RNAseq datasets of embryos from different ASD models, demonstrating that regions involved in neuronal development are affected. We evaluated the effect of prenatal treatment with resveratrol (RSV) on the neuronal organization and quantity of parvalbumin-positive (PV+), somatostatin-positive (SOM+), and calbindin-positive (CB+) GABAergic interneurons, besides the levels of synaptic proteins and GABA receptors in the medial prefrontal cortex (mPFC) and hippocampus (HC) of the ASD model induced by valproic acid (VPA). In summary, metabolic alterations or gene expression impairments could be induced by VPA, leading to extensive damage in the late developmental stages. By contrast, due to its antioxidant, neuroprotective, and opposite action on histone properties, RSV may avoid damages induced by VPA.

Mice homozygous for the nude mutation (Foxn1nu) are hairless and exhibit congenital dysgenesis of the thymic epithelium, resulting in a primary immunodeficiency of mature T-cells, and have been used for decades in research with tumor grafts. Here we investigate the impact of T-cell immunodeficiency on behaviours relevant to the study of neurodevelopmental and neuropsychiatric disorders.

Prenatal exposition to valproic acid diminished aquaporin 1 in the choroid plexus, in the primary somatosensory area, in the amygdala region, and in the medial prefrontal cortex, reduced aquaporin 4 in medial prefrontal cortex and increased aquaporin 4 levels in primary somatosensory area (with resveratrol prevention). Valproic acid exposition also increased the number of astrocytes and GFAP fluorescence in both primary somatosensory area and medial prefrontal cortex. In medial prefrontal cortex, resveratrol prevented the increased fluorescence. Finally, there was an effect of resveratrol per se on the number of astrocytes and GFAP fluorescence in the amygdala region and in the hippocampus. Thus, this work demonstrates significant changes in blood–brain barrier permeability, edema formation, distribution of aquaporin 1 and 4, in addition to astrocytes profile in the animal model of autism, as well as the use of resveratrol as a tool to investigate the mechanisms involved in the pathophysiology of autism spectrum disorder.