Differential regulation of hippocampal neurogenesis by nitric oxide following seizures

The fact that the adult brain is able to produce new neurons or glial cells from neural stem cells (NSC) became one of the most interesting and challenging fields of research in neuroscience. Endogenous adult neurogenesis occurs in two main regions of the brain: the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) in the dentate gyrus. Brain injury may be accompanied by increased neurogenesis, although neuroinflammation promotes the activation of microglial cells that can be detrimental to the neurogenic process. Nitric oxide (NO) is one of the factors released by microglia that can be proneurogenic. The mechanism by which NO promotes the proliferation of NSCs has been intensively studied. However, little is known about the role of NO in migration, survival and differentiation of the newborn cells. The aim of this work was to investigate the role of NO from inflammatory origin in proliferation, migration, differentiation and survival of NSCs from the dentate gyrus in a mouse model of status epilepticus. We also assessed neuroinflammation in the same injury model. Our work showed that NO increased proliferation of the early-born cells after seizures, but is detrimental for their survival. NO also increased migration of neuroblasts. Moreover, NO was important to maintain long-term neuroinflammation. Taken together, these results show that NO may be a good target to promote proliferation and migration of NSCs following seizures, but compromises survival of early-born cells.

Molecular characterization of Gla-rich protein (GRP) gene expression and function

Gla-rich protein (GRP) is a vitamin K-dependent protein related to bone and cartilage recently described. This protein is characterized by a large number of Gla (γ-carboxyglutamic acid) residues being the protein with the highest Gla content of any known protein. It was found in a widely variety of tissues but highest levels was found in skeletal and cartilaginous tissues. This small secreted protein was also expressed and accumulated in soft tissues and it was clearly associated with calcification pathologies in the same tissues. Although the biological importance of GRP remains to be elucidated, it was suggested a physiological role in cartilage development and calcification process during vertebrate skeleton formation. Using zebrafish, an accepted model to study skeletal development, we have described two grp paralog genes, grp1 and grp2, which exhibited distinct patterns of expression, suggesting different regulatory pathways for each gene. Gene synteny analysis showed that grp2 gene is more closely related to tetrapod grp, although grp1 gene was proposed to be the vertebrate ortholog by sequence comparison. In addition, we identified a functional promoter of grp2 gene and using a functional approach we confirmed the involvement of transcription factors from Sox family (Sox9b and Sox10) in the regulation of grp2 expression. In an effort to provide more information about the function of grp isoforms, we generated two zebrafish transgenic lines capable to overexpress conditionally grp genes and possible roles in the skeleton development were studied. To better understand GRP function a mammalian system was used and the analysis of knockout mice showed that GRP is involved in chondrocyte maturation and the absence of GRP is associated to proteoglycans loss in calcified articular cartilage. In addition, we detected differences in chondrogenesis markers in articular chondrocyte primary culture. Overall, our data suggest a main role for GRP on chondrocyte differentiation.

Cloning of the Bone Gla Protein gene from the teleost fish Sparus aurata (gilthead seabream). Molecular organization, developmental appearance and evolutionary implications

Tese de Doutoramento, Biologia Molecular, Faculdade de Ciências do Mar e do Ambiente, Universidade do Algarve, 2001

Antioxidant and phenolic compounds in sweet potato peels and leaves: food applications and health benefits

Tese de doutoramento, Ciências Biotecnológicas (Biotecnologia Alimentar), Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2014

Study of the expression of different genes of long-chain polyunsaturated fatty acids (LC-PUFA) metabolism during the early paralarval development of the common octopus (Octopus vulgaris)

Dissertação de mestrado, Aquacultura e Pescas, Faculdade de Ciências e Tecnologias, Universidade do Algarve, 2015

Development of non-viral vectors for gene therapy for pathologies of the retina

Tese de doutoramento, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015

Study of the association of Gla Rich Protein (GRP) to human blood cells

Dissertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Biomedicina, Universidade do Algarve, 2013

Desenvolvimento de filmes à base de quitosano com microencapsulação de agentes naturais: cinéticas de libertação

Dissertação de mestrado, Tecnologia de Alimentos, Instituto Superior de Engenharia, Universidade do Algarve, 2013

Locust bean gum-based microparticles for pulmonary delivery of antibiotics

Dissertação de Mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2016

Contribuição para o estudo de produção de azeitona de mesa da cultivar Cobrançosa: caraterização microbiológica

Dissertação de Mestrado, Tecnologia dos Alimentos, Instituto Superior de Engenharia, Universidade do Algarve, 2016

Contribuição para o estudo da produção de azeitona de mesa da cultivar Cobrançosa: caracterização físico-química, organolética e nutricional

Dissertação de Mestrado, Tecnologia dos Alimentos, Instituto Superior de Engenharia, Universidade do Algarve, 2016

Boronic acids as partners in multicomponent reactions

Tese de doutoramento, Farmácia (Química Farmacêutica e Terapêutica), Universidade de Lisboa, Faculdade de Farmácia, 2014

Human factors required for mycobacterium tuberculosis macrophage infection

Tese de doutoramento, Farmácia (Biologia Celular e Molecular), Universidade de Lisboa, Faculdade de Farmácia, 2014

Biological membranes : biophysical properties and aquaporin function

Tese de doutoramento, Farmácia (Bioquímica), Universidade de Lisboa, Faculdade de Farmácia, 2014

Calorimetric and mass spectrometric studies of ionic liquids

Tese de doutoramento, Química (Química-Física), Universidade de Lisboa, Faculdade de Ciências, 2014