Ethiane Segabinazi

Authorized SARS-CoV-2 vaccines elicit both antibody and T-cell responses; however, benchmark correlates and update decisions have largely emphasized neutralizing antibodies. Motivated by the complementary role of cellular immunity, we designed a prototype polyepitope DNA vaccine encoding conserved human and mouse T-cell epitopes from non-structural proteins of the original strain SARS-CoV-2 lineage. Epitope selection was guided by in silico predictions for common HLA class I alleles in the Brazilian population and the mouse H-2Kb haplotype. To enhance immunogenicity, the polyepitope sequences were fused to glycoprotein D (gD) from Herpes Simplex Virus 1 (HSV-1), an immune activator of dendritic cells (DCs), leading to enhanced activation of antigen-specific T-cell responses. Mice were immunized with two doses of the electroporated DNA vaccine encoding the gD-fused polyepitope, which induced robust interferon-gamma– and tumor necrosis factor-alpha–producing T cell responses compared to control mice. In addition, K18-hACE2 transgenic mice showed protection against intranasal challenge with the original SARS-CoV-2 strain, with reduced clinical symptoms, less weight loss, and decreased viral burden in both lung and brain tissues. The results experimentally confirm the protective role of T cells in vaccine-induced protection against SARS-CoV-2 and open perspectives for the development of universal anti-coronavirus vaccines.

Clinical studies show that physical exercise has anxiolytic and pro-cognitive properties for both healthy individuals and psychiatric patients. Most of these data refer to the effects of aerobic exercise. However, other modalities such as resistance exercise deserve more attention because they may also modulate brain function. This study aimed to compare the effects of an aerobic exercise protocol on a treadmill and a resistance exercise protocol on a ladder apparatus on anxiety-like behavior, cognitive flexibility, and neuroplasticity parameters in healthy animals. Adult male Wistar rats were divided into three groups: sedentary control, aerobic training, and resistance training. Subsequently, they were evaluated in the elevated plus-maze (EPM), light-dark box, and modified hole board (mHB) tests. The expressions of synaptophysin and postsynaptic plasticity protein 95 in the dorsal and ventral hippocampus were analyzed by immunofluorescence. The results demonstrated an anxiolytic effect promoted by exercise in the EPM, particularly in the animals submitted to aerobic training, and a mild pro-learning effect of both exercise modalities was observed in the mHB test. All groups showed similar outcomes in the other evaluations. Therefore, the exercise modalities investigated in the present study did not provide considerable modifications to such aspects of the emotional/cognitive functions and neuroplasticity under physiological contexts. Perhaps the two types of exercise acted in neurobiological pathways not analyzed in this study, or the effects may emerge under pathological contexts. These hypotheses should be tested in future studies.

Type 1 diabetes mellitus (T1DM) has been associated with long-term complications in the central nervous system, causing brain cellular dysfunctions and cognitive deficits. On the other hand, enriched environment (EE) induces experience-dependent plasticity, especially in the hippocampus, improving the performance of animals in learning and memory tasks. Thus, our objective was to investigate the influence of the EE on memory deficits, locomotion, corticosterone levels, synaptophysin (SYP) protein immunoreactivity, cell survival and microglial activation in the dentate gyrus (DG) of T1DM rat hippocampus. Male Wistar rats (21-day-old) were exposed to EE or maintained in standard housing (controls, C) for 3 months. At adulthood, the C and EE animals were randomly divided and diabetes was induced in half of them. All the animals received 4 doses of BrdU, 24 h apart. Hippocampus-dependent spatial memory, general locomotion and serum corticosterone levels were evaluated at the end of the experiment. The animals were transcardially perfused 30 days post-BrdU administration. Our results showed that EE was able to prevent/delay the development of memory deficits caused by diabetes in rats, however it did not revert the motor impairment observed in the diabetic group. SYP immunoreactivity was increased in the enriched healthy group. The EE decreased the serum corticosterone levels in diabetic adult rats and attenuated the injurious microglial activation, though without altering the decrease of the survival cell. Thus, EE was shown to help to ameliorate cognitive comorbidities associated with T1DM, possibly by reducing hyperactivity in the hypothalamic–pituitary–adrenal axis and microglial activation in diabetic animals.