Biology subjects

Figueiredo, C. P.

Publications and source records attributed to Figueiredo, C. P..

8 recordsLinked to original sources

bioRxiv2026

Acute IFN-gamma responses drive sensory neuron injury and chronic pain after chikungunya virus infection

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute and chronic musculoskeletal disease characterized by often debilitating pain; however, the mechanisms associated with the pain remain understudied. Here, we used an experimental mouse model and patients to investigate the role of interferon-{gamma} (IFN-{gamma}) in the pain during chronic inflammation after CHIKV infection. Our data show that CHIKV induces sustained joint inflammation, cartilage catabolism, and sensory neuron injury signatures, including Atf3 upregulation, but lacks detectable viral dissemination to dorsal root ganglia. We found that IFN-{gamma} expression was higher in CHIKV-infected joints, and direct IFN-{gamma} administration recapitulates mechanical hypersensitivity and neuronal stress independently of joint degeneration. Genetic or pharmacological disruption of IFN-{gamma} signalling prevented CHIKV-induced pain and neuronal stress without altering viral burden, demonstrating that IFN-{gamma} is required for both sensory dysfunction and joint pathology. By stratifying CHIKV-infected mice based on long-term nociceptive profiles, we show that persistent-pain subgroup characterized by elevated acute-phase systemic IFN-{gamma} and chronic peripheral neuropathic features. These findings were confirmed in human patients, where acute-phase IFN-{gamma} levels distinguished those who developed chronic arthralgia from those who recovered. Overall, our findings demonstrate that persistent post-CHIKV pain is driven by an IFN-{gamma}-mediated neuroimmune mechanism.

microbiology↗

bioRxiv2024

Mapping the Brazilian Scientific Diaspora: Migration Patterns of PhDs in Global Mobility

A scientific diaspora refers to a community of scientists who have emigrated from their home country to work in another nation. This study investigates this phenome in depth the Brazilian context, examining who comprises this diaspora (doctorates, postdocs, lecturers), where they have migrated, and their areas of study. We conducted this examination based on publications by Brazilian doctors who graduated between 2005 and 2021, as well as post-doctorates and students with full doctorate scholarships abroad. These students were identified on the CAPES open data website. The publications of these authors were captured in Scopus and Web of Science. Then those with addresses abroad were analysed in Vosviewer(R) and using logistic regression (stayed abroad or not), area of knowledge and a decision tree to see the effect of the Brazilian university region, type of institution and scholarship on the decision to migrate. The level of diaspora is approximately 1.7% among all doctorates trained in Brazil, reaching 6.6% in postdoctoral scholars with experience abroad. This suggests that PhDs with advanced training and experience have a higher propensity to emigrate from Brazil. These PhDs predominantly choose to migrate to North America and Western Europe, with a strong preference for careers in Science, Technology, Engineering, and Mathematics (STEM) fields. Brazilian PhDs with international experience tend to have a more diverse migration pattern, while those who complete their PhD in Brazil show a distinct preference for migrating to Portugal, indicating differing global mobility based on scientific experience. A decision tree analysis reveals that life or exact sciences PhDs, those who graduated after 2012, and obtained their postgraduate degrees from institutions in the southeast or south of Brazil are more likely to migrate. While the reasons behind these migration patterns are not evaluated in this study, better job prospects, higher salaries, or more substantial research funding could be influential factors in the decision to migrate.

scientific communication and education↗

bioRxiv2023

Histone deacetylase inhibition mitigates cognitive deficits and astrocyte dysfunction induced by Ab oligomers

Inhibitors of histone deacetylases (iHDACs) are promising drugs for neurodegenerative diseases. We have evaluated the therapeutic potential of the new iHDAC6 LASSBio-1911 in A{beta} oligomer (A{beta}O) toxicity models and astrocytes, key players in neuroinflammation and Alzheimers disease (AD). Astrocyte phenotype and synapse density were evaluated by flow cytometry, Western blotting, immunofluorescence and qPCR, in vitro and in mice. Cognitive function was evaluated by behavioural assays using a mouse model of intracerebroventricular infusion of A{beta}O. LASSBio-1911 modulates reactivity and synaptogenic potential of cultured astrocytes and improves synaptic markers in cultured neurons and in mice. It prevents A{beta}O-triggered astrocytic reactivity in mice and enhances the neuroprotective potential of astrocytes. LASSBio-1911 improves behavioural performance and rescues synaptic and memory function in A{beta}O-infused mice. These results contribute to unveiling the mechanisms underlying astrocyte role in AD and provide the rationale for using astrocytes as targets to new drugs for AD.

neuroscience↗

bioRxiv2022

Different outcomes of neonatal and adult Zika virus infection on startle reflex and prepulse inhibition in mice

Zika virus (ZIKV) infection causes severe neurological consequences in both gestationally-exposed infants and adults. Sensorial gating deficits strongly correlate to the motor, sensorial and cognitive impairments observed in ZIKV-infected patients. However, to date, no startle response or prepulse inhibition (PPI) assessment has been made in patients or animal models. In this study, we identified different outcomes for the age of infection and sex in wild-type mice: neonatally infected animals presented an increase in PPI and startle latency in both sexes, while adult infected males presented lower startle amplitude but preserved PPI. Our data further the understanding of the functional impacts of ZIKV on the developing and mature nervous system, which could help explain other behavioral and cognitive alterations caused by the virus. With this study, we support the use of startle reflex testing in ZIKV exposed patients, especially infants, allowing for early detection of functional neuromotor damage and early intervention.

neuroscience↗

bioRxiv2022

SARS-CoV-2 spike protein induces long-term TLR4-mediated synapse and cognitive loss recapitulating Post-COVID syndrome

Cognitive dysfunction is often reported in post-COVID patients, but its underlying mechanisms remain unknown. While some evidence indicate that SARS-CoV-2 can reach and directly impact the brain, others suggest viral neuroinvasion as a rare event. Independently of brain viral infection, the ability of SARS-CoV-2 spike (S) protein to cross the BBB and reach memory-related brain regions has already been shown. Here, we demonstrate that brain infusion of S protein in mice induces late cognitive impairment and increases serum levels of neurofilament light chain (NFL), which recapitulates post-COVID features. Neuroinflammation, hippocampal microgliosis and synapse loss are induced by S protein. Increased engulfment of hippocampal presynaptic terminals late after S protein brain infusion were found to temporally correlate with cognitive deficit in mice. Blockage of TLR4 signaling prevented S-associated detrimental effects on synapse and memory loss. In a cohort of 86 patients recovered from mild COVID-19, genotype GG TLR4 -2604G>A (rs10759931) was associated with poor cognitive outcome. Collectively, these findings indicate that S protein directly impacts the brain and suggest that TLR4 is a potential target to prevent post-COVID cognitive dysfunction. One Sentence SummaryTLR4 mediates long-term cognitive impairment in mice and its genetic variant increases the risk of poor cognitive outcome in post-COVID patients.

neuroscience↗

bioRxiv2020

Zika virus replicates in skeletal muscle contributing to peripheral viral amplification prior to reach neural tissue

Zika virus (ZIKV) infections are still a worldwide concern due to the severity of neurological outcomes. ZIKV neurotropism is well characterized, but peripheral tissue could be sites of viral amplification, contributing to endothelial-barrier crossing and access to peripheral nerves. During acute and late phases of infection, ZIKV can be detected in several body fluids, eyes, testis and vagina. However, the importance of initial replication sites for the establishment of infection and viral spread remain unknown. Here we demonstrated that ZIKV replicates primarily in human muscle precursor cells, resulting in cell death and inhibition of myogenesis. ZIKV also replicates in fetal muscle after maternal transmission and in infected neonate mice, inducing lesions and inflammation. Muscle was an important site of viral amplification, sustaining higher peripheral viral loads than liver and spleen. In addition, ZIKV showed rapid and sustained replication kinetics in muscle even before replication in the neural tissues, persisting until 16 days post infection. Our results highlight the importance of muscle in ZIKV pathogenesis as a peripheral site of viral amplification which may contribute to ZIKV reaching neural structures. Author SummaryZika Virus (ZIKV) neurotropism and its deleterious effects on central nervous system have been well characterized. But, investigations of the initial replication sites for the establishment of infection and viral spread to neural tissues remain under explored. Here we demonstrated that ZIKV replicates primarily in human skeletal muscle precursor cells, resulting in cell death and disrupted myogenesis. ZIKV also replicates in muscle of fetus and neonate mice inducing muscle damage and inflammation. Muscle replication occurs before amplification in peripheral nerves and brain, contributing to the increase of peripheral ZIKV load and dissemination. In addition, ZIKV RNA still been detected in skeletal muscle at late stages of infection. Overall, our findings showed that skeletal muscle is involved in ZIKV pathogenesis, contributing to a broader understanding of ZIKV infection. Thus, opens new aspects in the investigation of the long-term consequence of early infection.

microbiology↗

bioRxiv2019

Mayaro virus replication restriction and induction of muscular inflammation in mice are dependent on age and type-I interferon response

Mayaro virus (MAYV) is an emergent Arbovirus belonging to the Alphavirus genus from the Togaviridae family which has been circulated in forest regions of American continent through small outbreaks. Recent studies warned for the risk of MAYV dispersion to new areas and for the potential establishment of an urban epidemic cycle. Similar to Chikungunya and other arthritogenic Alphavirus, MAYV-induced disease shows a high prevalence of arthralgia and myalgia that can persist for months. Despite this, knowledge regarding pathogenesis, characteristics of host immune response, and resolution of MAYV infections are still limited. Here we investigated the dependence of age, innate and adaptive immunity for the control of MAYV replication and induction of inflammation in mice. We observed that age and type I interferon response are related to restriction of MAYV infection and tissue inflammation in mice. Moreover, we showed that MAYV continues to replicate persistently in adult recombination activation gene-1 efficient mice (RAG1-/-), indicating that adaptive immunity is essential to MAYV clearance. Despite chronic replication, infected adult RAG1-/- mice did not develop an apparent signal of muscle damage at late infection. On the other hand, MAYV infection induces muscular and paw inflammation in young WT and adult Type I Interferon receptor deficient mice (IFNAR-/-). In addition, MAYV infection triggers an increase in the expression of pro-inflammatory mediators, such as TNF, IL-6, KC, IL-1{beta}, MCP-1, and RANTES, in muscle tissue, and decreases TGF-{beta} expression. Taken together, our study contributes to the comprehension of MAYV pathogenesis, and describes a translational mouse model for further studies of MAYV infection, as well for testing vaccine and therapeutic strategies against this virus.\n\nAuthor SummaryMAYV-induced disease presents a high prevalence of arthralgia and myalgia that potentially persist for months, which is characteristic of the arthritogenic Alphavirus group. However, information regarding MAYV infection and the molecular mechanism of pathogenesis is still scarce. Here we investigated the dependence of age, innate and adaptive immunity for the control of MAYV replication and induction of inflammation in mice. We observed that tissue inflammation and the restriction of MAYV replication in mice are affected by aging and type I interferon response. Besides, we also showed that adaptive immunity was important for MAYV clearance in adult mice. Histological analyses demonstrated that MAYV replication triggered muscular and paw inflammation in young WT and adult type-I interferon receptor deficient mice. In addition, the level of expression of several pro-inflammatory cytokines was increased in the muscle MAYV-infected mice. Our data provide an advance for understanding the molecular mechanism involved in MAYV pathogenesis, as well as describes an in vivo model for further investigations on MAYV infection and for antiviral compounds and vaccine testing.

microbiology↗

bioRxiv2019

Yellow Fever Vaccine Protects Resistant and Susceptible Mice Against Zika Virus Infection

Zika virus (ZIKV) emerged as an important infectious disease agent in Brazil in 2016. Infection usually leads to mild symptoms but severe congenital neurological disorders and Guillain-Barre syndrome have been reported following ZIKV exposure. The development of an effective vaccine against Zika virus is a public health priority, encouraging the preclinical and clinical studies of different vaccine strategies. Here, we describe the protective effect of an already licensed attenuated yellow fever vaccine (17DD) on type-I interferon receptor knockout mice (A129) and immunocompetent (BALB/c) mice infected with ZIKV. Yellow fever virus vaccination results in robust protection against ZIKV, with decreased mortality in the A129 mice, a reduction in the cerebral viral load in all mice, and weight loss prevention in the BALB/c mice. Despite the limitation of yellow fever (17DD) vaccine to elicit antibody production and neutralizing activity against ZIKV, we found that YF immunization prevented the development of neurological impairment induced by intracerebral virus inoculation in adult. Although we used two vaccine doses in our protocol, a single dose was protective, reducing the cerebral viral load. Different Zika virus vaccine models have been tested; however, our work shows that an efficient and certified vaccine, available for use for several decades, effectively protects mice against Zika virus infection. These findings open the possibility for using an available and inexpensive vaccine to a large-scale immunization in the event of a Zika virus outbreak.

immunology↗