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History of FAPESP XI

A busy brain

Advances made in the field of neuroscience were encouraged by the Foundation

ARTHUR TOGA / UCLAArtistic rendering of brain functions: science maps the brain’s ability to adapt and regenerateARTHUR TOGA / UCLA

Studies that focus on how the brain functions have expanded their horizons in the last few decades. For example, studies have been conducted on the limits of the brain’s adaptation to traumas and environmental changes. FAPESP has collaborated extensively with the advances made in this field. The Inter-Institutional Cooperation for the Support of Brain Research (CinAPCe) is the Foundation’s latest initiative in this respect. The acronym alludes to the homonym “synapse,” the structure through which the nerve impulse travels from one neuron to the other. This network congregates groups from six São Paulo State institutions involved in different fields of knowledge. The project’s starting point was the acquisition of four high field magnetic resonance imaging machines, with twice as much power as older existing machines in Brazil. The new machines are being used to broaden studies being conducted on the mechanisms of epilepsy in the Brazilian population.

Nearly 20 thousand images on the functioning of the brain have already been captured by the machines. These images support the public and private hospitals that provide medical care for epileptics. “We have a significant number of complex images that will generate studies for many years,” says neurologist Fernando Cendes, head of the neuroimaging laboratory at the Medical School of the State University of Campinas (Unicamp), one of the creators of the project. Various papers on methodological issues have already been submitted to scientific publications, such as variations in the brain images – from different machines – of the same patient, or the influence of noise produced by magnetic resonance equipment on the results of the exams. The groups involved in the CInAPCe keep in touch by means of teleconferences, during which they plan and evaluate the task of analyzing various types of images obtained from the equipment. “Each group analyzes a category of images and now we are increasing the capacity of our computers so that we can run the information faster,” he says. According to Cendes, the importance of the program is not restricted to the scientific findings. “Some things are not visible in the short term. I am referring to the conditions of the structure being offered in relation to the training of researchers,” he adds.

The decision to elect epilepsy as the object of the study was a natural choice. Epilepsy had been extensively studied by the project participants. The CInAPCe program began to be created in the late 1990s, and took off as of 2007, through the acquisition of the equipment; each machine cost approximately US$ 2 million. One of the machines was acquired by the network’s private partner, namely the Israeli Institute of Study and Research, linked to São Paulo’s Albert Einstein Hospital. Three other machines were installed at the Medical School of Unicamp, at the Medical School of the University of São Paulo (FMUSP), in the city of São Paulo, and at the Medical School of the University of São Paulo (FMRP) in the city of Ribeirão Preto. The network also includes researchers from the University of São Paulo in the city of São Carlos. These researchers are conducting studies of experimental models on rats and apes. The Federal University of São Paulo (Unifesp), which has a long-standing tradition in basic research on epilepsy, is also a member of the network.

The selection of these institutions was based on their tradition of conducting research on neuroscience and on their training programs for researchers. FMUSP, for example, has dedicated itself to experimental neurology for many decades. The first steps in this respect were taken by such professors as Eros Abrantes Enhart and Orlando Aidar, neuroanatomists from the 1950s interested in the regenerative capacity of the nervous system. “ They have always fostered students’  interest in research, and many professors from FMUSP were influenced by them,” says professor Gerson Chadi, who teaches experimental neurology and is the head of FMUSP’s neurosurgical physiopathology laboratory, also known as LIM45. Chadi’s research work, which focuses on neuronal plasticity and regeneration, is funded by FAPESP. Chadi has also received grants from the Foundation to attend two post-doctorate programs, one in Sweden and the other one in Canada. By resorting to experimental models for neurodegenerative diseases and to clinical projects, namely, several recent projects funded by FAPESP, Chadi has mobilized a number of research groups to motivate translational neuroscience, which bridges the gap between the laboratory bench and the patient’s hospital bed. “The first papers on this topic have already been published,” he says.

PERSONAL FILEAntonio Spina França, from USP, and Rita Levi Montalcini, Nobel laureate for Medicine, meeting in Brazil in 1986PERSONAL FILE

Gerson Chadi highlights the name of Antonio Spina França Netto (1927-2010), professor emeritus at the FMUSP’s department of neurology, who was part of the generation that followed Eros and Aidar. França Netto was involved in doing research on cerebrospinal fluid and neurological infections. “He implemented the concept of conducting lab investigations whose results would provide patients with more immediate benefits, generally in the form of diagnosis or by increasing the knowledge of the people involved ,” he states. In the mid 1980s, research on neurology, renamed neuroscience, moved significantly forward, thanks to the adoption of molecular biology methods, Chadi says. “Progress in this area led to the identification of new molecules and communication mechanisms among neurons and their surrounding cells. This opened up the way to various research possibilities on the central nervous system’s ability to regenerate,” says the researcher. An example in this respect was the identification of the nervous cells’  growth factor, such factor having been identified by Italy’s Rita Levi Montalcini – who is now 103 years old. Rita Montalcini was the laureate of the Nobel Prize for Medicine in 1987. She had scientific contacts with professor Spina França and opened the doors for him to collaborate with other European researchers. Another prominent name among USP professors was Cesar Timo-Iaria (1925-2005), a specialist in electrophysiology, who helped train a generation of researchers, such as Miguel Nicolelis, a professor at Duke University, and Koichi Sameshima, a professor at FMUSP’s radiology department, among others. Timo-Iaria made several important contributions. He proved that blood sugar concentration, that is, the concentration of glucose in the blood, is regulated by a neural system comprised of sensitive neurons called glicoceptors. He also proved that hunger is not triggered by hypoglycemia, but by the liver’s metabolic work to prevent blood sugar levels from going down.

USP’s Medical School of Ribeirão Preto, which is also participating in the CInAPCe program, produced such prominent researchers as Miguel Covian (1913-1992), an Argentine who moved to Brazil in the 1950s. He was one of the pioneers in the field of neurophysiology in Latin America, and studied under Bernardo Houssay, the Argentine researcher who was the Nobel Prize for Medicine or Physiology laureate in 1947. Frederico Graeff was another prominent researcher; he was a specialist in neuropsychopharmacology and conducted leading studies on anxiety and panic disorders.

At Unifesp, the former Paulista School of Medicine, research studies on neuroscience were developed by two professors, José Ribeiro do Vale and José Leal Prado, who trained researchers such as Elisaldo Carlini, founder of the psychobiology department and creator of the Brazilian Center for Information on Psychotropic Drugs (Cebrid) research center. Sergio Tufik, one of the world’s foremost specialists on sleep disorders and coordinator of the Center for Sleep Studies, was one of his students. The Center for Sleep Studies is one of the 11 Centers of Research, Innovation, and Diffusion (Cepid), funded by FAPESP. Tufik was supervised by Argentine’s Miguel Covian during his master’s degree program and by Carlini during his doctorate program. Argentine neuroscientist Iván Izquierdo worked at Unifesp in the 1970s and then continued his academic career in the State of Rio Grande do Sul, at the Federal University and at the Catholic University. Izquierdo also planted the seeds that would bloom at the São Paulo State institution. Esper Abrão Cavalheiro, one of the students supervised by Izquierdo during the master’s degree and doctorate program, specialized in epilepsy and developed an experimental model currently being used in the United States, England, France, Germany, Italy, Japan and Australia. The model, created together with Poland’s Lechoslaw Turski, is a method that induces convulsions in lab animals. The animals are given pilocarpine, an alkaloid extracted from the leaves of the jaborandi, a native Brazilian shrub. Cavalheiro is one of the leading users of FAPESP’s funding instruments to foster international collaboration (see Pesquisa FAPESP issue no. 181).

Luiz Eugênio Mello, a professor at Unifesp’s department of physiology and director of the Vale Technological Institute, says that the Foundation’s financial support of research studies on neuroscience is not only measured by grandiose projects. “There is a long list of researchers who have made significant contributions in this field and whose career paths were influenced by FAPESP,” he says, referring to such prominent researchers as Jair Mari, of Unifesp, Wagner Gattaz, Valentim Gentil Filho, Dora Ventura and Cesar Ades, of USP. “I wouldn´t have been able to do a fraction of what I did if it hadn’t been for FAPESP,” says Mello, former assistant coordinator of FAPESP’s Office of the Science Director in the period from 2003 to 2006. Professor Mello is currently doing research in the field of neuronal plasticity, basic acupuncture mechanisms and epilepsy, among others.