Leptin Prevents Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of Dopamine Receptors

Depression is a chronic and recurrent disorder, associated with high morbidity and risk of suicide. Leptin was firstly described as an anti-obesity hormone, but several actions of leptin in CNS have been reported. In fact, leptin regulates dopaminergic neurotransmission in mesolimbic areas and has antidepressant-like properties in stress-based models. In the present study, we investigated, for the first time, putative antidepressant-like effects of leptin in an animal model of depressive-like behaviors induced by lipopolysaccharide (LPS), and the potential involvement of dopamine receptors as mediators of those behavioral effects. Mice were injected leptin (1.5 mg/kg, IP) or imipramine prior to LPS administration. To evaluate the involvement of dopamine receptors, different experimental groups were pretreated with either the dopaminergic antagonist SCH23390, for D1 receptors or raclopride, for D2/D3 receptors, prior to leptin injection. Twenty-four hours post-LPS, mice were submitted to the forced swimming and sucrose preference tests. In addition, IL-1β levels were determined in the prefrontal cortex (PFC), hippocampus and striatum. BDNF levels were measured in the hippocampus. Our results showed that leptin, similarly to imipramine, prevented the core behavioral alterations induced by LPS (despair-like behavior and anhedonia), without altering locomotion. In neurochemical analysis, leptin restored LPS-induced changes in IL-1β levels in the PFC and striatum, and increased BDNF levels in the hippocampus. The blockade of dopamine D1 and D2/D3 receptors inhibited leptin's antidepressant-like effects, whilst only the blockade of D1-like receptors blunted leptin-induced increments in prefrontal IL-1β levels. Our results indicate that leptin has antidepressant-like effects in an inflammatory model of depression with the contribution, at least partial, of dopamine receptors

Mucosal immunization with PspA (Pneumococcal surface protein A)-adsorbed nanoparticles targeting the lungs for protection against pneumococcal infection

Burden of pneumonia caused by Streptococcus pneumoniae remains high despite the availability of conjugate vaccines. Mucosal immunization targeting the lungs is an attractive alternative for the induction of local immune responses to improve protection against pneumonia. Our group had previously described the development of poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL) polymeric nanoparticles (NPs) adsorbed with Pneumococcal surface protein A from clade 4 (PspA4Pro) within L-leucine microcarriers (nanocomposite microparticles-NCMPs) for mucosal delivery targeting the lungs (NP/NCMP PspA4Pro). NP/NCMP PspA4Pro was now used for immunization of mice. Inoculation of this formulation induced anti-PspA4Pro IgG antibodies in serum and lungs. Analysis of binding of serum IgG to intact bacteria showed efficient binding to bacteria expressing PspA from clades 3, 4 and 5 (family 2), but no binding to bacteria expressing PspA from clades 1 and 2 (family 1) was observed. Both mucosal immunization with NP/NCMP PspA4Pro and subcutaneous injection of the protein elicited partial protection against intranasal lethal pneumococcal challenge with a serotype 3 strain expressing PspA from clade 5 (PspA5). Although similar survival levels were observed for mucosal immunization with NP/NCMP PspA4Pro and subcutaneous immunization with purified protein, NP/NCMP PspA4Pro induced earlier control of the infection. Conversely, neither immunization with NP/NCMP PspA4Pro nor subcutaneous immunization with purified protein reduced bacterial burden in the lungs after challenge with a serotype 19F strain expressing PspA from clade 1 (PspA1). Mucosal immunization with NP/NCMP PspA4Pro targeting the lungs is thus able to induce local and systemic antibodies, conferring protection only against a strain expressing PspA from the homologous family 2

Mental health and burnout syndrome among postgraduate students in medical and multidisciplinary residencies during the COVID-19 pandemic in Brazil : protocol for a prospective cohort study

Background: The COVID-19 pandemic has led to high levels of physical, psychological, and social stress among health care professionals, including postgraduate students in medical and multidisciplinary residencies. This stress is associated with the intense fear of occupational exposure to SARS-CoV-2, the virus known to cause COVID-19. These professionals are at risk of developing physical and mental illnesses not only due to the infection but also due to prolonged exposure to multidimensional stress and continued work overload. Objective: This study aims to evaluate the prevalence of symptoms suggestive of mental disorders and burnout syndrome and determine the risk factors for burnout among postgraduate students in medical and multidisciplinary residencies in Brazil during the COVID-19 pandemic. Methods: For this prospective cohort study with parallel groups, participants were recruited between July and September 2020 to achieve a sample size of at least 1144 participants. Research instruments such as Depression, Anxiety, and Stress Scale; Patient Health Questionnaire; Brief Resilient Coping Scale; and Oldenburg Burnout Inventory will be used to collect data. Data will be collected in 2 waves: the first wave will include data related to sample characterization and psychosocial evaluation, and the second wave will be launched 12 weeks later and will include an evaluation of the incidence of burnout as well as correlations with the potential predictive factors collected in the first wave. Additionally, we will collect data regarding participants’ withdrawal from work. Results: The recruitment took place from July 29 to September 5, 2020. Data analyses for this phase is already in progress. The second phase of the study is also in progress. The final data collection began on December 1, 2020, and it will be completed by December 31, 2020. Conclusions: We believe the findings of this study will help evaluate the impact of the COVID-19 pandemic on the mental health conditions of health professionals in Brazil as well as contribute to the planning and implementation of appropriate measures that can alleviate these mental health challenges. International Registered Report Identifier (IRRID): DERR1-10.2196/2429