Neuronal counting and parasympathetic dysfunction in the hearts of chronically Trypanosoma cruzi - infected rats

Ten male Wistar rats, chronically infected with Colombian, São Felipe (12SF) and Y strains of Trypanosoma cruzi and ten non-infected control animals were submitted to the bradycardia responsiveness test, an assessment of heart parasympathetic function, after phenylephrine injection. Six chagasic animals showed heart parasympathetic dysfuntion characterized by reduction in the index of bradycardia baroreflex responsiveness, as compared with the control group. Microscopic examination of the atrial heart ganglia of chagasic rats showed ganglionitis, but no statiscally significant reduction in the number of neurons.

On the analytical solutions of the Hindmarsh-Rose neuronal model

In this article we analytically solve the Hindmarsh-Rose model (Proc R Soc Lond B221:87-102, 1984) by means of a technique developed for strongly nonlinear problems-the step homotopy analysis method. This analytical algorithm, based on a modification of the standard homotopy analysis method, allows us to obtain a one-parameter family of explicit series solutions for the studied neuronal model. The Hindmarsh-Rose system represents a paradigmatic example of models developed to qualitatively reproduce the electrical activity of cell membranes. By using the homotopy solutions, we investigate the dynamical effect of two chosen biologically meaningful bifurcation parameters: the injected current I and the parameter r, representing the ratio of time scales between spiking (fast dynamics) and resting (slow dynamics). The auxiliary parameter involved in the analytical method provides us with an elegant way to ensure convergent series solutions of the neuronal model. Our analytical results are found to be in excellent agreement with the numerical simulations.

Dissecting neuronal development deficits by inflammation: from morphology to cytoskeleton dynamics

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Desenvolvimento de suportes biodegradáveis para regeneração do tecido neuronal

Dissertação para obtenção do Grau de Mestre em Engenharia Biomédica

Suportes porosos com topografia de fibras alinhadas para a regeneração neuronal

Dissertação para obtenção do Grau de Mestre em Engenharia Biomédica

Dissecting neuronal dysfunction and microglia/motoneurons cross-talk in ALS: an immunofluorescence directed study

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Despopulação neuronal pancreática em chagásicos crônicos

Revendo a literatura não encontramos estudos anatômicos dos gânglios intrapancreáticos na forma crônica da doença de Chagas; lesões dos mesmos poderiam explicar, ao menos em parte, os distúrbios funcionais do pâncreas exócrino e endócrino descritos nesta forma da doença. Decidimos então analisar morfologicamente tais gânglios. Para isso, estudamos segmentos transversais da cabeça, corpo e cauda do pâncreas de doze chagásicos crônicos, com idade média de 46,5 ± 9,1 anos, e quatorze controles, com idade média de 41,2 ± 11,0 anos. Os segmentos foram processados histologicamente e seccionados de forma seriada até o esgotamento, analisando-se os cortes múltiplos de sete. Para análise estatística, usamos o teste não-paramétrico de Mann-Whitney. Na cabeça do pâncreas, a contagem de neurônios teve média de 57,3 ± 50,8 para o grupo chagásico e 117,5 ± 99,0 para o grupo controle (p < 0,05); no corpo, 25,9 ± 19,4 para o grupo chagásico e 54,7 ± 47,8 para o controle (p < 0,05); na cauda, 23,4 ± 16,3 para o chagásico e 54,1 ± 29,2 para o controle (p < 0,01), sendo a contagem total de 106,6 ± 71,1 para o chagásico e 226,3 ± 156,5 para o controle (p < 0,01). Nossos achados nos permitiram concluir que: a) ocorreu despopulação neuronal estatisticamente significante no grupo chagásico em relação ao controle, em cada segmento pancreático analisado, bem como no órgão como um todo; b) 50% dos chagásicos tiveram número total de neurônios inferior ao menor número dos controles (80); c) 75% e 91,6% dos chagásicos tiveram número de neurônios inferior, respectivamente, à mediana (171) e à média (226) do grupo controle; d) assim, a despopulação neuronal pancreática foi frequente, porém não constante; e) o fator idade não pareceu ter sido o responsável pela despopulação neuronal dos chagásicos.

Despopulação neuronal cardíaca em hamsters (Mesocricetus auratus) cronicamente infectados com o Trypanosoma cruzi

Com o objetivo de se obter um modelo experimental que permitisse estabelecer a despopulação (desnervação) neuronal cardíaca procurou-se pesquisar o comportamento do sistema nervoso intracardíaco em hamsters cronicamente infectados com o T. cruzi. Para tal fim, realizaram-se contagens dos neurônios do plexo nervoso autonômico intracardíaco em hamsters inoculados com 35.000 formas sangüíneas de três cepas diferentes, sacrificados 5, 8 e 10 meses depois da infecção. Demonstrou-se, pela primeira vez, destruição neuronal significativa num modelo experimental, similar à que ocorre na doença de Chagas humana.

Migration and differentiation of neuronal precursors in the postnatal brain: insights from the subventricular zone and cerebellum

Fundação para a Ciência e a Tecnologia - SFRH/BD/42848/2008, através do Programa MIT_Portugal em Sistemas de Bioengenharia; projectos PTDC/SAUNEU/104415/2008 e Projecto ref. 96542 da Fundação Caloust Gulbenkian

Dissecting gastrointestinal dysfunction and inflammation in a “pre-motor” rodent model of Parkinson’s disease

Research on Parkinson’s disease (PD) has mainly focused on the degeneration of the dopaminergic neurons of nigro-striatal (NS) pathway; also, post-mortem studies have demonstrated that the noradrenergic and the serotonergic transmitter systems are also affected (Jellinger, 1999). Degeneration of these neuronal cell bodies is generally thought to start prior to the loss of dopaminergic neurons in the NS pathway and precedes the appearance of the motor symptoms that are the “hallmark” of PD. Gastrointestinal (GI) motility is often disturbed in PD, manifesting chiefly as impaired gastric emptying and constipation. These GI dysfunction symptoms may be the result of a loss in noradrenergic and serotonergic innervation. GI deficits were evaluated using an organ bath technique. Groups treated with different combinations of neurotoxins (6-OHDA alone, 6-OHDA + pCA or 6-OHDA + DSP-4) presented significant differences in gut contractility compared to control groups. Since a substantial body of literature suggests the presence of an inflammatory process in parkinsonian state (Whitton, 2007), changes in pro-inflammatory cytokines in the gut were assessed using a cytokine microarray. It has been found in this work that groups with a combined dopaminergic and noradrenergic lesion have a significant increase in both expressions of IL-13 and VEGF. IL-6 also shows a decrease in treatment groups; however this decrease did not reach statistical significance. The therapeutic value of Exendin-4 (EX-4) was evaluated. It has been previously demonstrated that EX-4, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is neuroprotective in rodent models of PD (Harkavyi et al., 2008). In this thesis it has been found that EX-4 was able to reverse a decrease in gut contractility obtained through intracerebral bilateral 6-OHDA injection. Although more studies are required, EX-4 could be used as a possible therapy for the GI symptoms prominent in the early stages of PD.

The Role of the Fbox Protein CG6758 in Xbp1s Induced Retinal Degeneration in Drosophila

The Unfolded Protein Response (UPR) is a signaling pathway that is activated by an accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) that causes ER stress. The activation of the UPR aims to restore ER homeostasis by attenuation of ER client protein translation, increased transcription of ER chaperones and ER associated degradation (ERAD) factors. If ER stress is too long or too strong, cells may die. The main signaling branch of the UPR is mediated by the ER transmembrane protein IRE1 and the transcription factor Xbp1. The active, spliced form of Xbp1 (Xbp1spliced) acts as a transcription factor with protective function against toxic protein aggregation. However, overexpression of Xbp1spliced in the developing Drosophila eye causes degeneration of the eye (“glossy” eye phenotype).(...)

Bacterial cellulose as a novel substrate for retinal pigment epithelium cells transplantation in age-related macular degeneration

Tese de Doutoramento em Engenharia Química e Biológica.

Desenvolvimento de rede neuronal artificial para o diagnóstico de doenças neurodegenerativas

Dissertação de mestrado integrado em Engenharia Eletrónica Industrial e Computadores

Mitral valve repair. Quadrangular resection of the posterior leaflet in patients with myxomatous degeneration

OBJECTIVE - To analyze the immediate and late results of mitral valve repair with quadrangular resection of the posterior leaflet without the use of a prosthetic ring annuloplasty. METHODS - Using this technique, 118 patients with mitral valve prolapse who underwent mitral repair from January '84 through December '96 were studied. Age ranged from 30 to 86 (mean = 59.1±11.8) years and 62.7% were males. An associated surgery was performed in 22% of the patients, and coronary artery bypass graft was the most frequently performed surgery (15 patients - 12.7%). In 20 (16.9%) patients other associated techniques of mitral valve repair were used and shortening of elongated chordae tendineae was the most frequent one (6 patients). RESULTS - Immediate mortality was 0.9% (one patient). Long-term rates for thromboembolism, endocarditis, re-operation and death in the late postoperative period were 0.4%, 0.4%, 1.7% and 2.2% patients/year, respectively. The actuarial curve of survival was 83.8±8.6% over 12 years; survival free from re-operation was 91.8±4.3%, free from endocarditis was 99.2±0.8% and free from thromboembolism was 99.2±0.8%. In the late postoperative period, 93.8% of the patients were in functional class 1 (NYHA), with a complete follow-up in 89.7% of the patients. CONCLUSION - Patients with mitral valve prolapse who undergo mitral valve repair using this technique have a satisfactory prognosis over 12 years.