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

Management and recovery of an urbanized catchment.

Divulga os resultados do mapeamento, utilizando geoprocessamento, da Bacia Hidrográfica de Servidão, em Rio Claro-S

Sudden cardiac death in epilepsy disappoints, but epileptologists keep faith

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in people with intractable epilepsy. Probably, optimization of seizure control will prevent some of these deaths. Briefly, we integrated in this paper some data about the epidemiology, risk factors, etiology, and preventative measures in the management of SUDEP.FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)CNPq (Conselho National de Desenvolvimento Cientifico e Tecnologico)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), CEPID/FAPESPFAPESP/PRONEXFAPESP/CNPq/MCT (Instituto Nacional de Neurociencia Translational)Univ Fed Sao Paulo, Escola Paulista Med, Disciplina Neurociencia, Dept Neurol Neurocirurgia, Sao Paulo, SP, BrazilPontificia Univ Catolica Rio Grande do Sul, Hosp Sao Lucas, Porto, BrazilPontificia Univ Catolica Rio Grande do Sul, Inst Cerebro Rio Grande Sul, Serv Neurol, Porto, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Disciplina Neurociencia, Dept Neurol Neurocirurgia, Sao Paulo, SP, BrazilWeb of Scienc

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

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

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

Intraspecific variability of dihydrochalcone, chromenes and benzoic acid derivatives in leaves of Piper aduncum L.(Piperaceae)

Chemical analysis carried out in leaves of 18 specimens of Piper aduncum L. (Piperaceae) occurring at Ripasa Reserve, Araraquara, SP, Brazil indicated two distinct populations when investigated over aperiod of 14 months (January 2000 to February 2001) and then submitted to cluster analysis. The two groups were characterized by accumulation of prenylated benzoic acids, chromenes and dihydrochalcone, respectively. A total of seven compounds were identified by HPLC analysis and compared with standards including two prenylated benzoic acid [aduncumene (1) and 3-(3’-7’-dimethyl- 2’-6’-octadienyl)-4-methoxy-benzoic acid (5)], four chromenes [methyl 2,2-dimethyl-8-(3’-methyl-2’-butenyl)-2H-1-chromene-6-carboxylate (4), methyl 2,2-dimethyl-2H-1-chromene-6-carboxylate (2b), methyl 8-hydroxy-2,2-dimethyl-2H-1-chromene-6-carboxylate (3) and 2,2-dimethyl-2H-1-chromene-6- carboxylic acid (2a)] and one dihydrochalcone [2’,6’-dihydroxy-4’-methoxy- dihydrochalcone (6)]

Respiration, Oxidative Phosphorylation, And Uncoupling Protein In Candida Albicans.

The respiration, membrane potential (Deltapsi), and oxidative phosphorylation of mitochondria in situ were determined in spheroplasts obtained from Candida albicans control strain ATCC 90028 by lyticase treatment. Mitochondria in situ were able to phosphorylate externally added ADP (200 microM) in the presence of 0.05% BSA. Mitochondria in situ generated and sustained stable mitochondrial Deltapsi respiring on 5 mM NAD-linked substrates, 5 mM succinate, or 100 microM N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride plus 1 mM ascorbate. Rotenone (4 microM) inhibited respiration by 30% and 2 micro M antimycin A or myxothiazole and 1 mM cyanide inhibited it by 85%. Cyanide-insensitive respiration was partially blocked by 2 mM benzohydroxamic acid, suggesting the presence of an alternative oxidase. Candida albicans mitochondria in situ presented a carboxyatractyloside-insensitive increase of Deltapsi induced by 5 mM ATP and 0.5% BSA, and Deltapsi decrease induced by 10 microM linoleic acid, both suggesting the existence of an uncoupling protein. The presence of this protein was subsequently confirmed by immunodetection and respiration experiments with isolated mitochondria. In conclusion, Candida albicans ATCC 90028 possesses an alternative electron transfer chain and alternative oxidase, both absent in animal cells. These pathways can be exceptional targets for the design of new chemotherapeutic agents. Blockage of these respiratory pathways together with inhibition of the uncoupling protein (another potential target for drug design) could lead to increased production of reactive oxygen species, dysfunction of Candida mitochondria, and possibly to oxidative cell death.371455-6