Natural regulatory (CD4+CD25+FOXP+) T cells control the production of pro-inflammatory cytokines during Plasmodium chabaudi adami infection and do not contribute to immune evasion.

Different functions have been attributed to natural regulatory CD4+CD25+FOXP+ (Treg) cells during malaria infection. Herein, we assessed the role for Treg cells during infections with lethal (DS) and non-lethal (DK) Plasmodium chabaudi adami parasites, comparing the levels of parasitemia, inflammation and anaemia. Independent of parasite virulence, the population of splenic Treg cells expanded during infection, and the absolute numbers of activated CD69+ Treg cells were higher in DS-infected mice. In vivo depletion of CD25+ T cells, which eliminated 80% of CD4+FOXP3+CD25+ T cells and 60–70% of CD4+FOXP3+ T cells, significantly decreased the number of CD69+ Treg cells in mice with lethal malaria. As a result, higher parasite burden and morbidity were measured in the latter, whereas the kinetics of infection with non-lethal parasites remained unaffected. In the absence of Treg cells, parasite-specific IFN-γ responses by CD4+ T cells increased significantly, both in mice with lethal and non-lethal infections, whereas IL-2 production was only stimulated in mice with non-lethal malaria. Following the depletion of CD25+ T cells, the production of IL-10 by CD90− cells was also enhanced in infected mice. Interestingly, a potent induction of TNF- and IFN-γ production by CD4+ and CD90− lymphocytes was measured in DS-infected mice, which also suffered severe anaemia earlier than non-depleted infected controls. Taken together, our data suggest that the expansion and activation of natural Treg cells represent a counter-regulatory response to the overwhelming inflammation associated with lethal P.c. adami. This response to infection involves TH1 lymphocytes as well as cells from the innate immune system

Pesquisas em epilepsia 150 anos após a teoria da evolução de Darwin

On February 12, 2009, we commemorated the 200th anniversary of Charles Darwin's birth and the 150th anniversary of the publication of the ûrst edition of the "On the origin of species". Only in the sixth edition of the Origin Darwin explicitly stated that natural selection applied to the brain as to all other organs and contemporary epilepsy research plays an interesting role in this scenario. Epilepsy affects approximately 3 percent of the general population and is a complex disease. At least 11 genes have now been described for human epilepsy and over 50 more genes have been identified in animal models of epilepsy. The complex gene to gene interactions and gene-environment interactions may account for epilepsy susceptibility and antiepileptic drug response. Darwin's thoughts on evolution are relevant to understand these gene interactions, contributing to current development of new treatments and prevention of chronic diseases, such as epilepsy.Em 12 de Fevereiro de 2009 nós comemoramos o aniversário de 200 anos de Charles Darwin e os 150 anos da publicação da primeira edição do livro "A Origem das Espécies". Apenas na sexta edição do livro A Origem, Darwin explicitamente definiu que a seleção natural se aplicava ao cérebro, assim como a todos os outros órgãos e as pesquisas contemporâneas em epilepsia tem um papel interessante neste cenário. A epilepsia afeta aproximadamente 3% da população geral e é uma doença complexa. Ao menos 11 genes foram descritos até o momento na epilepsia humana e mais de 50 genes foram identificados em modelos animais de epilepsia. As complexas interações gene-gene e genes-meio ambiente podem estar relacionadas com a susceptibilidade à epilepsia e respostas às drogas antiepilépticas. Os pensamentos de Darwin quanto à evolução são relevantes para a compreensão dessas interações gênicas, contribuindo para o desenvolvimento de novos tratamentos e na prevenção de doenças crônicas, como a epilepsia.FAPESPCInAPCe-FAPESPCNP

Quantification of respiratory parameters in patients with temporal lobe epilepsy

Dysfunction affecting cardiac or pulmonary systems has been postulated as a major factor in sudden death in epilepsy (SUDEP). Whilst the majority of studies of cardiorespiratory function have focused on changes during seizures, here we investigate whether epilepsy influences basal respiratory parameters in patients with temporal lobe epilepsy (TLE) during the interictal period. Spirometry was performed in 10 females and 10 males. Measurements of Vital Capacity (VC), Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1) and ratios of FEV1 to FVC (FEV1/FVC) were obtained, and these values were analyzed as percentages of predicted values. None of the patients had chronic obstructive pulmonary disease and no significant alterations in respiratory function tests were found among these patients. No association between seizure frequency, antiepileptic drugs and SUDEP could be found in this study. Although the study did not identify any specific respiratory abnormality in TLE patients during the interictal period, re-evaluation of clinical data on pulmonary disorders in people with epilepsy should be better investigated

Melanin-Concentrating Hormone (MCH): Role in REM Sleep and Depression.

The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator synthesized by neurons of the lateral sector of the posterior hypothalamus and zona incerta. MCHergic neurons project throughout the central nervous system, including areas such as the dorsal (DR) and median (MR) raphe nuclei, which are involved in the control of sleep and mood. Major Depression (MD) is a prevalent psychiatric disease diagnosed on the basis of symptomatic criteria such as sadness or melancholia, guilt, irritability, and anhedonia. A short REM sleep latency (i.e., the interval between sleep onset and the first REM sleep period), as well as an increase in the duration of REM sleep and the density of rapid-eye movements during this state, are considered important biological markers of depression. The fact that the greatest firing rate of MCHergic neurons occurs during REM sleep and that optogenetic stimulation of these neurons induces sleep, tends to indicate that MCH plays a critical role in the generation and maintenance of sleep, especially REM sleep. In addition, the acute microinjection of MCH into the DR promotes REM sleep, while immunoneutralization of this peptide within the DR decreases the time spent in this state. Moreover, microinjections of MCH into either the DR or MR promote a depressive-like behavior. In the DR, this effect is prevented by the systemic administration of antidepressant drugs (either fluoxetine or nortriptyline) and blocked by the intra-DR microinjection of a specific MCH receptor antagonist. Using electrophysiological and microdialysis techniques we demonstrated also that MCH decreases the activity of serotonergic DR neurons. Therefore, there are substantive experimental data suggesting that the MCHergic system plays a role in the control of REM sleep and, in addition, in the pathophysiology of depression. Consequently, in the present report, we summarize and evaluate the current data and hypotheses related to the role of MCH in REM sleep and MD

Epilepsia e morte súbita?: Coma mais peixe! A hipótese de um grupo

Epilepsy is the commonest serious neurological disorder and individuals with epilepsy are at higher risk of death than the general population and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures play a potential role. The ultimate goal of SUDEP research is to develop methods to prevent it and nutritional aspects such as omega-3 fatty acid deficiency may have an interesting role in this scenario. Omega-3 fatty acids reduce the risk of cardiovascular mortality and are important for treating or preventing some neurological diseases, including epilepsy. A dietary modification or nutritional supplements increasing the ingestion of omega-3 fatty acids may help to ''save the brain".A epilepsia é uma das doenças neurológicas sérias mais comuns e está associada a um maior risco de morte do que o observado na população geral e a morte súbita em epilepsia é uma importante causa de morte relacionada à epilepsia. Os potenciais patomecanismos da morte súbita em epilepsia são desconhecidos, mas é bastante provável que arritmias cardíacas durante ou entre as crises tenham um papel preponderante. O objetivo final das pesquisas em morte súbita em epilepsia é o desenvolvimento de métodos que levem à sua prevenção e aspectos nutricionais, como a deficiência de ômega-3 pode ter um papel interessante neste contexto. A suplementação com ômega-3 reduz o risco de mortalidade de origem cardiovascular e é importante no tratamento e prevenção de algumas doenças neurológicas, incluindo a epilepsia. A modificação dietética ou a suplementação nutricional aumentando a ingesta de ômega-3 pode ajudar a "salvar o cérebro".FAPESPCInAPCe-FAPESPINCT/MCT Ministério de Ciência e TecnologiaCNP