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As Ligas Acadêmicas exercem papel fundamental nas universidades, com atividades extracurriculares que expandem o conhecimento dos alunos integrantes além da graduação, contemplando também o meio acadêmico e a sociedade. O processo pioneiro de implantar uma Liga Acadêmica em um campus em implantação é um grande desafio. A Liga Acadêmica de Anatomia do Campus UFRJ-Macaé (Laanamac) objetiva estimular a interação dos alunos, desenvolver projetos de pesquisa, extensão e ensino, e ser modelo para a criação de novas ligas. Este trabalho relata o primeiro ano da Laanamac e os resultados alcançados: maior interesse dos alunos pela Anatomia, possibilidade de ingresso em uma Iniciação científica, dissecação de cadáveres, interação com docentes e discentes de outras instituições, desenvolvimento de habilidades como gerenciamento de uma liga e organização de eventos, e divulgação do nome da instituição em congressos. Uma liga recém-formada pode contribuir de forma significativa no desenvolvimento de novos campi, por ampliar as possibilidades, principalmente, dos que estão se estabelecendo longe das grandes cidades.

The Academic Leagues play a fundamental role in universities, offering extracurricular activities that expand students’ knowledge beyond undergraduate learning, including academia and society. However, the pioneering process of implementing an Academic League at a campus under construction is a great challenge. The Academic League Anatomy of the UFRJ Macaé Campus (Laanamac) aims to encourage student interaction, develop research, community outreach and teaching projects and to be a model for the creation of new leagues. This paper reports on the first year of Laanamac and its achievements, such as increased student interest in anatomy, the opportunity to partake in a Scientific Initiation, the dissection of corpses, interaction with teachers and students from other institutions, the development of skills such as league management and organization of events, and the promotion of the institution’s name at congresses. A newly formed league can add significantly to the development of new campuses, by opening up new possibilities, especially for those who are establishing themselves far from the big cities.

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Glial cells are currently viewed as active partners of neurons in synapse formation. The close proximity of astrocytes to the synaptic cleft suggests that these cells might be potential targets for neuronal-released molecules although this issue has been less addressed. Here, we evaluated the role of the excitatory neurotransmitter, glutamate, in astrocyte differentiation. We recently demonstrated that cortical neurons activate the gene promoter of the astrocyte maturation marker, GFAP (glial fibrillary acidic protein) of cerebral cortex astrocytes by inducing TGF-beta1 (transforming growth factor beta 1) secretion in vitro. To access the effect of glutamate on GFAP gene, we used transgenic mice bearing the beta-Galactosidase (beta-Gal) reporter gene under the regulation of the GFAP gene promoter. We report that 100 muM glutamate activates the GFAP gene promoter of astrocytes from cerebral cortex revealed by a significant increase in the number of beta-Gal positive astrocytes. Neutralizing antibodies against TGF-beta completely prevented glutamate and neuronal-induction of GFAP gene, thus indicating that this event is mediated by TGF-beta1. Further, induction of GFAP gene in response to glutamate was followed by nuclear translocation of the Smad transcription factor, a hallmark of TGF-beta1 pathway activation. The antagonist of the metabotropic glutamate receptor, MCPG, inhibited neuronal effect suggesting that neuronal activation of GFAP gene promoter involves glutamate metabotropic receptors. MAPK (PD98059) and PI3K (LY294002) inhibitors fully prevented activation of GFAP gene promoter by all treatments. Surprisingly, these inhibitors also abrogated TGF-beta1 direct action on GFAP gene although they did not inhibit Smad-2 phosphorylation, suggesting that TGF-beta1-induced GFAP gene activation might involve cooperation between the canonical and non-canonical TGF-beta pathways. Together, our results suggest that glial metabotropic glutamate 2/3 receptor activation by neurons induces TGF-beta1 secretion, leading to GFAP gene activation and astrocyte differentiation and involves Smad and MAPK/PI3K pathways. Our work provides evidence that astrocytes surrounding synapses are target of neuronal activity and might shed light into the role of glial cells into neurological disorders associated with glutamate neurotoxicity.

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The transforming growth factor-betas (TGF-betas) comprise a family of pleiotropic members that signal through two types of serine/threonine kinase receptors, named TGFRI (TGF-beta type I receptor) and TGFRII (TGF-beta type II receptor). We previously demonstrated that cortical neurons increase the astrocyte maturation marker, glial fibrillary acidic protein (GFAP), and thus, astrocyte differentiation, by inducing TGF-beta1 secretion by astrocytes in vitro. Although TGF-beta receptor expression has been described in different brain regions and cell types, their localization is still a subject of discussion. In the present work, we analyzed TGFRII expression in cultured cortical astrocytes from embryonic and newborn animals by immunocytochemistry, Western blot, and reverse transcriptase-polymerase chain reaction (RT-PCR). We report for the first time expression of TGFRII in embryonic glia. TGFRII immunostaining was punctual and spread throughout the cellular membrane of embryonic and newborn astrocytes. Western blot and RT-PCR assays revealed similar levels of the receptor in astrocytes from different ages. Identification of TGFRII in embryonic astrocytes is novel and might point to the multipotent precursor cell, radial glia, as a potential target for TGFbeta1 during astrocyte development.

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Transforming growth factor betas (TGF-betas) are known as multifunctional growth factors, which participate in the regulation of key events of development, disease and tissue repair. In central nervous system (CNS), TGF-beta1 has been widely recognized as an injury-related cytokine, specially associated with astrocyte scar formation in response to brain injury. TGF-betas family is represented by three isoforms: TGF-beta1, -beta 2 and -beta 3, all produced by both glial and neuronal cells. They are involved in essential tissue functions, including cell-cycle control, regulation of early development and differentiation, neuron survival and astrocyte differentiation. TGF-beta signaling is mediated mainly by two serine threonine kinase receptors, TGFRI and TGFRII, which activate Smad 2/3 and Smad 4 transcription factors. Phosphorylation and activation of these proteins is followed by formation of Smad 2/3-4 complex, which translocates to the nucleus regulating transcriptional responses to TGF-beta. Very few data are available concerning the intracellular pathway required for the effect of TGF-beta in brain cells. Recently, emerging data on TGF-beta1 and its signaling molecules have been suggesting that besides its role in brain injury, TGF-beta1 might be a crucial regulator of CNS development. In this review, we will focus on TGF-betas members, specially TGF-beta1, in neuron and astrocyte development. We will discuss some advances concerning the emerging scenario of TGF-beta1 and its signaling pathways as putative modulators of astrocyte biology and their implications as a novel mediator of cellular interactions in the CNS.

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The expression of glial fibrillary acidic protein (GFAP), the major intermediate filament protein of mature astrocytes, is regulated under developmental and pathological conditions. Recently, we have investigated GFAP gene modulation by using a transgenic mouse bearing part of the GFAP gene promoter linked to the beta-galactosidase reporter gene. We demonstrated that cerebral cortex neurons activate the GFAP gene promoter, inducing transforming growth factor-beta 1 (TGF-beta 1) secretion by astrocytes. Here, we report that cortical neurons or conditioned medium derived from them do not activate the GFAP gene promoter of transgenic astrocytes derived from midbrain and cerebellum suggesting a neuroanatomical regional specificity of this phenomenon. Surprisingly, they do induce synthesis of TGF-beta 1 by these cells. Western blot and immunocytochemistry assays revealed wild distribution of TGF receptor in all subpopulations of astrocytes and expression of TGF-beta 1 in neurons derived from all regions, thus indicating that the unresponsiveness of the cerebellar and midbrain GFAP gene to TGF-beta 1 is not due to a defect in TGF-beta 1 signalling. Together, our data highlight the great complexity of neuron-glia interactions and might suggest a distinct mechanism underlying modulation of the GFAP gene in the heterogeneous population of astrocytes throughout the central nervous system.

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