Perder peso melhora a memória e a concentração

Leveza para a memória

Pesquisadores descobriram uma ligação entre a perda de peso e a melhoria da memória e da concentração.

O estudo mostra que pacientes submetidos à cirurgia bariátrica apresentaram uma melhora significativa na memória 12 semanas após a cirurgia.

"A ideia inicial [da pesquisa] veio do nosso trabalho clínico," conta John Gunstad, da Universidade Kent, nos Estados Unidos. "Tive a oportunidade de trabalhar com um grande número de pessoas que estavam tentando perder peso, quer através de meios comportamentais ou por meio da cirurgia."

Testes cognitivos

Gunstad conta ter observado que os dois grupos de pacientes cometem erros semelhantes em testes cognitivos, o que os faz cair para uma faixa abaixo do considerado normal para a população como um todo.

Contudo, os pacientes submetidos à cirurgia bariátrica apresentaram uma melhoria da memória e da concentração 12 semanas após a cirurgia, melhorando seus resultados dos testes cognitivos - na média, eles passaram do nível "ligeiramente deficiente", antes da cirurgia, para "normal" depois da cirurgia.

"A principal motivação para estudar os pacientes da cirurgia é que sabemos que eles perdem muito peso em um curto espaço de tempo, então é um bom grupo para estudar", disse Gunstad. "Este é o primeiro indício de que, ao passar por esta cirurgia, as pessoas podem melhorar sua memória, concentração e capacidade de resolução de problemas."

Razões mentais para a perda de peso

Os cientistas afirmam que os resultados dão muitas razões para otimismo porque, ao contrário de outras condições médicas, a obesidade pode ser cuidada e revertida.

"Muitos dos fatores que acompanham a obesidade - tais como pressão alta, diabetes tipo 2 e apneia do sono - podem danificar o cérebro, mas são de certa forma reversíveis," disse Gunstad. "Como esses problemas desaparecem, o funcionamento da memória fica melhor."

Ao mostrar que os efeitos da obesidade também são reversíveis, as pessoas podem encontrar razões mais fortes que as levem a lutar contra o excesso de peso - a melhoria do funcionamento da mente, com eventuais melhorias no rendimento nos estudos, no trabalho, ou mesmo no dia-a-dia, parece ser uma razão forte o bastante.

Saúde do cérebro e do coração

A equipe agora vai acompanhar os participantes do estudo por dois anos, aferindo se os ganhos cognitivos se mantêm, se voltam a cair ou mesmo se melhoram ainda mais com o passar do tempo.

"Uma das coisas que nós sabemos é que, conforme os indivíduos se tornam mais saudáveis do ponto de vista cardiovascular, a saúde do seu cérebro também melhora," conclui Gunstad.

Recycling Within Amyloid-Beta Fibrils Might Be a Clue to the Cause of Alzheimer’s Disease

ScienceDaily (Apr. 13, 2011) — A research study, published recently in the Journal of the American Chemical Society (JACS), demonstrates that the aggregation of amyloid-beta (Aβ) proteins into amyloid fibrils characteristic of Alzheimer's disease (AD) is not irreversible, as previously thought. The Aβ protein molecules that comprise the fibrils are continuously detaching from and re-attaching to the fibrils, resulting in molecular recycling. These findings suggest that recycling could be a source of small non-fibrillar Aβ aggregates, which are believed to be responsible for the neurodegeneration observed in AD. The authors of this study, experts in protein structure and aggregation at IRB Barcelona and other research centers, led by the ICREA researcher Nàtalia Carulla, believe that modulation of fibril recycling may lead to the development of new therapeutic approaches to treat this disease.

Initial Aß40 molecules dissociate and reassociate through both ends of the fibrils faster than the Aß42 molecules (Initial molecules: grey circles; recycled molecules: orange circles).

New insights into the dynamics of amyloid fibrils

AD is a progressive neurodegenerative disease characterized by the presence of amyloid plaques in the brain. Previous analysis of these plaques revealed that their main constituents are fibrillar aggregates of the Aβ protein known as amyloid fibrils. This is the reason why initial studies proposed that Aβ fibrils caused the disease. Later, it was observed that there were only weak correlations between levels of amyloid fibrils in the brain and the severity of dementia. This finding led to the formulation of new hypotheses in which small Aβ protein aggregates formed before the development of fibrils are thought to be responsible for neurodegeneration. Recent data have shown that fibrillar plaques are a potential reservoir of small toxic Aβ protein aggregates. In this scenario, "understanding the molecular basis of the disease requires knowledge about the interconversion between the different species present during Aβ protein aggregation," says Carulla.

The team of researchers at IRB Barcelona has now characterized molecular recycling of two Aβ proteins, Aβ40 and Aβ42, the latter being the most associated with AD. After monitoring recycling during 40 days using hydrogen/deuterium exchange experiments, they found that Aβ40 and Aβ42 molecules recycle within the fibril population, although to different extents: after 40 days, 80 % of the molecules making up Aβ40 fibrils underwent recycling while only 30 % did so in Aβ42 fibrils. These observations imply that Aβ42 recycles more slowly.

"In the context of AD, demonstrating that recycling occurs in the fibrils is a step forward but it is also crucial to identify the recycling species involved; whether they are individual Aβ units or small aggregates made of several units," explains Carulla. "It will be important to address if differences in the recycling species within Aβ40 and Aβ42 fibrils are relevant in the development of Alzheimer's disease. We are now working towards this aim," emphasized Carulla. "Once we have this information, we will be in a position to devise new therapeutic strategies that can modulate recycling."

Patients' Own Cells Yield New Insights Into the Biology of Schizophrenia

ScienceDaily (Apr. 13, 2011) — After a century of studying the causes of schizophrenia-the most persistent disabling condition among adults-the cause of the disorder remains unknown. Now induced pluripotent stem cells (iPSCs) generated from schizophrenic patients have brought researchers from the Salk Institute for Biological Studies a step closer to a fundamental understanding of the biological underpinnings of the disease.

In this microscopic image, nuclei originated from human cells are stained red and stem-cell-derived newborn neurons are stained green.

In their study, published in the April 13, 2011 advance online issue of the journal Nature, the Salk team reports both that neurons generated from these patient-derived iPSCs made fewer connections with each other, and that Loxapine, an antipsychotic drug commonly used to treat schizophrenia, restored neuronal connectivity in iPSC neurons from all patients.

"This is the first time that a complex mental disease has been modeled in live human cells," says lead author Fred Gage, Ph.D., a professor in the Salk's Laboratory of Genetics and holder of the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Diseases. "This model not only affords us the opportunity to look at live neurons from schizophrenia patients and healthy individuals to understand more about the disease mechanism, but also to screen for drugs that may be effective in reversing it."

Schizophrenia, which is defined by a combination of paranoid delusions, auditory hallucinations and diminished cognitive function, afflicts one percent of the population worldwide, corresponding to nearly three million people in the United States alone. Accumulating genomic evidence indicates that many different combinations of genetic lesions-some of them affecting the susceptibility to environmental influences-may lead to a variety of signs and symptoms collectively labeled schizophrenia.

"Schizophrenia exemplifies many of the research challenges posed by complex psychiatric disorders," says Gage. "Without a basic understanding of the causes and the pathophysiology of the disorder, we lack the tools to develop effective treatments or take preventive measures."

Trying to overcome the limitations of the past, such as limited accessibility of human neurons and the difficulty of separating genetic and environmental influences, postdoctoral researcher and first author, Kristen Brennand, reprogrammed into iPSCs skin fibroblasts from four schizophrenia patients with a hereditary history of the disease. She then differentiated these cells into neurons.

"Nobody knows how much the environment contributes to the disease," she explains. "By growing neurons in a dish, we can take the environment out of the equation, and start focusing on the underlying biological problems."

But it wasn't till Brennand used a modified rabies virus, developed by Salk professors Edward Callaway and John Young, to highlight the connections between neurons that she was able to detect differences between normal neurons and neurons originating from schizophrenia patients. "It was really reassuring that in most ways, these 'schizophrenic' neurons are in fact indistinguishable from normal ones," she says.

The viral tracer made it apparent that the schizophrenic neurons connected less frequently with each other and had fewer projections growing out from their cell bodies. In addition, gene expression profiles identified almost 600 genes whose activity was misregulated in these neurons; 25 percent of those genes had been implicated in schizophrenia before.

Brennand then administered a number of frequently prescribed antipsychotic medications for the final three weeks of neuronal differentiation to test their ability to improve connectivity in vitro. Only Loxapine, which like all other currently FDA-approved schizophrenia medications acts on dopamine receptors in the brain, increased neurons' ability to reach out and connect with their neighbors. It also affected the activity of hundreds of genes.

"These drugs are doing a lot more than we thought they were doing," explains Brennand. "But now, for the very first time, we have a model system that allows us to study how antipsychotic drugs work in live, genetically identical neurons from patients with known clinical outcomes, and we can start correlating pharmacological effects with symptoms."

"For many years, mental illness has been thought of as a social or environmental disease, and many thought that if affected people just worked through their problems, they could overcome them," says Gage. "What we are showing are real biological dysfunctions in neurons that are independent of the environment."

Researchers who contributed to the study include Anthony Simone, Jessica Jou, Chelsea Gelboin-Burkhart, Ngoc Tran, Sarah Sangar, Yan Li, Yanglin Mu and Diana Yu in the Gage Laboratory; Gong Chen in the Department of Biology at Pennsylvania State University; Shane McCarthy at the Cold Spring Harbor Laboratory in Cold Spring Harbor, NY; and Jonathan Sebat at the University of California, San Diego.

The work was funded in part by the California Institute for Regenerative Medicine, the Lookout Foundation, Mathers Foundation, Helmsley Foundation and Sanofi-Aventis.

Potential New Strategy to Reduce Catheter Blockage

ScienceDaily (Apr. 13, 2011) — Bacterial genes that make urine less acidic could be good targets to prevent catheter blockage, according to research presented at the Society for General Microbiology's Spring Conference in Harrogate. The findings could lead to new strategies to prevent serious infections, particularly in long-term catheterization patients.

This is a phase contrast micrograph of a multicellular raft of P. mirabilis swarmer cells migrating over LB agar.

Urinary catheters are devices used in hospitals and community care homes to manage a range of bladder conditions, and are commonly used to manage incontinence in elderly individuals for long periods of time. Scientists from the University of Brighton, led by Dr Brian Jones, are looking at the bacterium Proteus mirabilis -- a common cause of urinary tract infections in patients undergoing long-term catheterization, which often leads to serious complications.

P. mirabilis cells can stick together on catheter surfaces where they form highly organized communities called biofilms. As the bacterium breaks down urea (using the enzyme urease) it causes the pH of urine to rise, leading to the formation of insoluble crystals which become trapped in the growing biofilm. The crystalline deposits can form a crust on the catheter and may eventually block urine flow from the bladder. If unnoticed, catheter blockage can lead to kidney and bloodstream infections, which ultimately may result in potentially fatal septic shock.

The team is identifying genes involved in P. mirabilis biofilm formation, and assessing their contribution to catheter blockage. The results show that biofilm-forming ability may be less important to catheter blockage than previously thought, and suggest that inhibiting the rise in urinary pH is a primary target for preventing catheter blockage. Nina Holling who is carrying out the research said, "In our experiments we have found biofilm-forming ability not to be the most important factor in catheter blockage. Although biofilm formation does play a role, the ability of P. mirabilis to increase urinary pH and form crystals seems to compensate for deficiencies in biofilm formation. However, much more work is required to fully understand the progression of these infections and biofilm formation may be more important in the early stages of infection."

Ms Holling explained the significance of the team's work. "Long-term catheterization is linked with an increased mortality rate among nursing home patients, and effective strategies to control these infections are urgently required," she said. "A greater understanding of how P. mirabilis forms biofilms and behaves within them will be important in developing such strategies. In the longer term, this would greatly benefit patients undergoing long-term catheterization by eliminating painful recurrent infections, which greatly reduce quality of life. In addition, the financial savings to the NHS would be significant."

Mechanism of Long-Term Memory Identified

ScienceDaily (Apr. 13, 2011) — Using advanced imaging technology, scientists from the Florida campus of The Scripps Research Institute have identified a change in chemical influx into a specific set of neurons in the common fruit fly that is fundamental to long-term memory.

Researchers have identified a change in chemical influx into a specific set of neurons in the common fruit fly that is fundamental to long-term memory. 

The study was published in the April 13, 2011 issue of The Journal of Neuroscience.

"In studying fruit flies' learning and long-term memory storage, we observed an increase in calcium influx into a specific set of brain neurons in normal fruit flies that was absent in 26 different mutants known to impair long-term memory,," said Ron Davis, chair of the Scripps Research Department of Neuroscience, who led the study. "This logical conclusion is that this increase, which we call a memory trace, is a signature component of long-term memory."

The memory trace in question is an increased influx of calcium into a set of neurons after long-term memory forms in a part of the insect brain known as mushroom bodies, a pair of oversized lobes known to mediate learning and memory, particularly the memories of smell. They have been compared to the hippocampus, a site of memory formation in humans.

Increases in calcium influx also occur with learning in other animal models, Davis said, and it seems highly likely a similar correlation exists in humans.

Measuring Memory Traces

To measure the changes in the Drosophila neurons, Davis and his colleagues used functional optical imaging, an advanced technology that his laboratory helped pioneer for the study of learning and memory. Using protein sensors that become fluorescent when calcium levels are increased, the team was able to highlight changes in the levels of calcium influx into the mushroom body neurons in response to odor learning. These observed memory traces occur in parallel with behavioral changes.

Interestingly, these memory traces occur only with spaced conditioning -- where the insects receive multiple episodes of learning but with periods of rest between each episode. Spaced conditioning is required for long-term memories to form.

In an earlier study last December, also published in TheJournal of Neuroscience, Davis found not only that fruit flies receiving spaced conditioning exhibited a long-term memory trace, but also that their memories lasted between four and seven days. In flies that were given a single episode of learning, memory formation lasted only a day and the long-term memory trace failed to form. These two studies are the newest in a series of six studies on the topic, including those published in the journal Neuron in 2004 and 2006, Cell in 2005, and Nature Neuroscience in 2008. Davis reviewed all of his studies of memory traces in the most recent issue of Neuron.

"The phenomenon of spaced conditioning is conserved across all species," Davis said. "No one really knows why it's important to long-term memory formation but there appears to be something magical about that rest period during learning."

The study was supported by the National Institutes of Health.