{"id":111736,"date":"2013-04-01T14:05:14","date_gmt":"2013-04-01T17:05:14","guid":{"rendered":"http:\/\/revistapesquisa.fapesp.br\/?p=111736"},"modified":"2017-03-07T15:11:47","modified_gmt":"2017-03-07T18:11:47","slug":"todays-superstars","status":"publish","type":"post","link":"https:\/\/revistapesquisa.fapesp.br\/en\/todays-superstars\/","title":{"rendered":"Today\u2019s superstars"},"content":{"rendered":"
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luan diniz \/ ufrj<\/span>Creating networks: a protein secreted by astrocytes…luan diniz \/ ufrj<\/span><\/p><\/div>\n

Long considered but secondary agents in the workings of the brain, glial cells only came to the fore over the last few years as research began to show their importance in the development, regeneration and structuring of the nervous system. Almost half of the brain\u2019s cells are glia \u2013 the others are neurons \u2013 and recent studies have associated their malfunctioning with neurodegenerative diseases.\u00a0 Researchers at the Federal University of Rio de Janeiro (UFRJ) have now discovered yet another important function of the glial cell. The biology research team of Fl\u00e1via Alcantara Gomes found that astrocytes, the most common of the glial cells, control the connections (synapses) between neurons, the cells that transmit and store information in the brain.<\/p>\n

\u201cWithout the glial cells, most of the synapses wouldn\u2019t work efficiently,\u201d says Gomes. In an article in the October 10, 2012 issue of the Journal of Biological Chemistry, <\/i>Gomes and her colleagues demonstrate that a protein produced in abundance by the astrocytes\u2013 the transforming growth factor \u00df1 (TGF-\u00df1) \u2013 regulates the formation of synapses in mice and humans. For Gomes, the discovery presents new perspectives to better understand the role of glia in the development of neurological disturbances and the aging process. There is evidence that during the initial stages of some diseases and of aging, neurons, before they begin to die out, start to detach from one another.<\/p>\n

The role of astrocytes in the formation of synapses has been suspected for some time. Approximately 10 years ago, Ben Barres, Frank Pfrieger and their colleagues at California\u2019s Stanford University reported that neurons in laboratory mice generated more synapses when in the presence of astrocytes. The researchers went on to identify certain synapse-forming molecules secreted by these astrocytes. These molecules, however, merely stimulate the formation of the chemical cleft or the structure whereby neurons pass signals on to other cells, and where neurotransmission might not have functioned properly.<\/p>\n

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LUAN DINIZ \/ UFRJ<\/span>… induces the formation of synapses, the colored specks on the neuronsLUAN DINIZ \/ UFRJ<\/span><\/p><\/div>\n

The UFRJ team showed that the TGF-\u00df1 is able to do both things: induce the formation of these structures and of functionally active synapses. \u201cWe take two paths to the same conclusion,\u201d Gomes explains. \u201cOne is a biochemical study using an in vitro <\/i>model, and the other is an analysis to identify the electric currents typical of synapses.\u201d<\/p>\n

As the nervous system develops during its embryonic stage, the glial cells of the cerebral cortex function as stem cells. In adults, these glial cells of the nervous system can create neural cells as well as astrocytes. UFRJ researchers had already discovered that the TGF-\u00df1 induced the differentiation of progenitor stem cells in astrocytes, but not in neurons. The current research study has determined that the TGF-\u00df1 generated by the astrocytes plays a new role. Neurons grown in cultures with this protein generate at least three times more synapses than those grown in the media of normal cultures. The same occurs when the TGF-\u00df1 is injected directly into the cortices of live animals.<\/p>\n

The team demonstrated that the role of the TGF-\u00df1 in forming synapses in the cerebral cortex is really an indirect one. The TGF-\u00df1 activates production of the D-serine amino acid (a compound made up of proteins), which is secreted by the neuron and then adheres to the neurotransmitter glutamine (see infographic<\/a><\/em>).\u00a0 Together, D-serine and glutamate activate the production of synapses in the neuron. The more D-serine there is present, the greater the number of synapses.<\/p>\n

Now in humans<\/b>
\n\u201cThe great merit of this research is, first of all, to show how astrocytes work biochemically to form the synapse and, second, to demonstrate this with cells derived from human tissue,\u201d says neuroscientist Luiz Roberto Giorgetti de Britto of the University of S\u00e3o Paulo (USP). This is because, up to now, studies that examine the complex relationship between neurons and astrocytes have been carried out only in mice, not humans.<\/p>\n

In the case of the human tissue trial, the team extracted astrocytes from the discarded brain tissue of epileptic patients who had undergone surgery at the UFRJ University Hospital. \u201cAs the human brain is more complex and difficult to work with, we have no standard procedures in place,\u201d explains Gomes. The results were similar, demonstrating that, biochemically, the human cells behave just like the astrocytes of mice.<\/p>\n

\"044-045_sinapse_204\"\u201cOur work is the result of a multidisciplinary scientific collaboration among diverse basic research and clinical research teams,\u201d says Gomes. On this note, the team is currently studying whether astrocytes from animal models or Alzheimer\u2019s disease or from patients with epilepsy has the potential to induce the formation of synapses.\u00a0\u00a0\u00a0\u00a0 In parallel, the team plans a similar test with astrocytes from patients with schizophrenia.<\/p>\n

\u201cCognitive ability in humans is associated with the complex of synaptic connections,\u201d says Gomes. She then adds, \u201cIt follows that dysfunctions in processing information in the brain can lead to serious neurological disorders. Understanding the mechanism by which synapses are formed and regulated is a key step to understanding the brain and developing therapies to repair the nervous system.\u201d<\/p>\n

Scientific article<\/em>
\nDINIZ, L.P. et al<\/em>. Astrocyte-induced synaptogenesis is mediated by transforming growth factor beta signaling through modulation of D-serine levels in cerebral cortex neurons<\/a>. Journal of Biological Chemistry<\/strong>. v. 287 (49), p. 41.432-45. 30 November 2012.<\/p>\n","protected":false},"excerpt":{"rendered":"Neighboring cells help neurons establish connections with one another","protected":false},"author":471,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[159],"tags":[250],"coauthors":[781],"class_list":["post-111736","post","type-post","status-publish","format-standard","hentry","category-science","tag-neuroscience"],"acf":[],"_links":{"self":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/111736","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/users\/471"}],"replies":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/comments?post=111736"}],"version-history":[{"count":0,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/111736\/revisions"}],"wp:attachment":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/media?parent=111736"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/categories?post=111736"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/tags?post=111736"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/coauthors?post=111736"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}