Animal models of intellectual disability: towards a translational approach

Intellectual disability is a prevalent form of cognitive impairment, affecting 2–3% of the general population. It is a daunting societal problem characterized by significant limitations both in intellectual functioning and in adaptive behavior as expressed in conceptual, social and practical adaptive skills. Intellectual disability is a clinically important disorder for which the etiology and pathogenesis are still poorly understood. Moreover, although tremendous progress has been made, pharmacological intervention is still currently non-existent and therapeutic strategies remain limited. Studies in humans have a very limited capacity to explain basic mechanisms of this condition. In this sense, animal models have been invaluable in intellectual disability investigation. Certainly, a great deal of the knowledge that has improved our understanding of several pathologies has derived from appropriate animal models. Moreover, to improve human health, scientific discoveries must be translated into practical applications. Translational research specifically aims at taking basic scientific discoveries and best practices to benefit the lives of people in our communities. In this context, the challenge that basic science research needs to meet is to make use of a comparative approach to benefit the most from what each animal model can tell us. Intellectual disability results from many different genetic and environmental insults. Taken together, the present review will describe several animal models of potential intellectual disability risk factors

Psychoanalysis and its role in brain plasticity: much more than a simple bla, bla, bla

Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Because scientists are unable to explain the unexplained, screening for cardiovascular abnormalities is a good method to protect against sudden unexpected death in patients with epilepsy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade Federal de São Paulo (UNIFESP) Departamento de FisiologiaUniversidade de São Paulo Faculdade de Medicina Hospital das ClínicasUNIFESP, EPMUNIFESP, Depto. de FisiologiaSciEL

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

Profile of neurologists in Brazil: a glimpse into the future of epilepsy and sudden unexpected death in epilepsy

Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de Neurologia ExperimentalUNIFESP, EPM, Disciplina de Neurologia ExperimentalSciEL

A utilidade do ácido graxo ômega-3 na epilepsia: mais do que uma criação de tilápias!

The epilepsies are one of the most common serious brain disorders and 20 to 30% of people developing epilepsy continue to have seizures and are refractory to treatment with the currently available therapies. Approximately one in a 1000 patients with chronic epilepsy will die suddenly, unexpectedly, and without explanation, even with post-mortem examination and this phenomenon is called sudden unexplained death in epilepsy (SUDEP). Understanding the mechanisms underlying SUDEP may lead to the identification of previously unrecognized risk factors that are more amenable to correction. We discuss here the possible implications of omega-3 fatty acids consumption on SUDEP prevention.As epilepsias encontram-se entre as mais sérias doenças neurológicas; 20 a 30% dos pacientes com epilepsia continuam apresentando crises e são refratários as terapias disponíveis atualmente. Aproximadamente um em cada 1000 pacientes com epilepsia crônica irá morrer de forma súbita, não esperada e sem explicação, mesmo com o exame pós-morte. Este fenômeno é denominado morte súbita e inesperada em epilepsia (SUDEP). Compreender os mecanismos envolvidos nos casos de SUDEP pode levar à identificação de fatores ainda não reconhecidos e passíveis de serem corrigidos. Discutiremos a seguir as possíveis implicações do consumo do ácido graxo ômega-3 na prevenção dos casos de SUDEP.CNPqFAPESP - CInAPCeFAEP

Thalamic nuclear abnormalities as a contributory factor in sudden cardiac deaths among patients with schizophrenia

Patients with schizophrenia have a two- to three-fold increased risk of premature death as compared to patients without this disease. It has been established that patients with schizophrenia are at a high risk of developing cardiovascular disease. Moreover, an important issue that has not yet been explored is a possible existence of a “cerebral” focus that could trigger sudden cardiac death in patients with schizophrenia. Along these lines, several structural and functional alterations in the thalamic complex are evident in patients with schizophrenia and have been correlated with the symptoms manifested by these patients. With regard to abnormalities on the cellular and molecular level, previous studies have shown that schizophrenic patients have fewer neuronal projections from the thalamus to the prefrontal cortex as well as a reduced number of neurons, a reduced volume of either the entire thalamus or its subnuclei, and abnormal glutamate signaling. According to the glutamate hypothesis of schizophrenia, hypofunctional corticostriatal and striatothalamic projections are directly involved in the pathophysiology of the disease. Animal and post-mortem studies have provided a large amount of evidence that links the sudden unexpected death in epilepsy (SUDEP) that occurs in patients with schizophrenia and epilepsy to thalamic changes. Based on the results of these prior studies, it is clear that further research regarding the relationship between the thalamus and sudden cardiac death is of vital importance

The brain-heart connection: Implications for understanding sudden unexpected death in epilepsy

Epilepsy is one of the commonest neurological problems worldwide. Approximately 3% of the general population will suffer from epilepsy at some point in their lives. Unfortunately, individuals with epilepsy are at a 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. Information concerning risk factors for SUDEP is conflicting, but potential risk factors include young age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure frequency, antiepileptic drug number and winter temperatures. Although the cause of SUDEP is still unknown, its most commonly suggested mechanisms are cardiac abnormalities during and between seizures. As the anatomical substrate of epileptic activity in the central nervous system shows a direct relation to cardiovascular alterations, this may suggest that patients with epilepsy associated with focal central nervous system lesions may face a particular risk of SUDEP. Currently, experimental and clinical data supports the importance of specific brain structures in the behavioural manifestation, the initiation and the propagation of seizures. Regarding the above findings, our research group focused on this review article that SUDEP could be related to the occurrence of specific brain structure dysfunction or anatomical change, at least in some cases