Foram enfocadas neste presente estudo, 3 raças de cães, ou seja, Boxer, Dobermann e Rottweiler, com tipos constitucionais e aptidões funcionais característicos e distintos entre si, sendo coletados 4 encéfalos de cada raça. Dos encéfalos foram retirados fragmentos das diferentes áreas do córtex cerebral, que foram preparados segundo técnica histológica convencional e corados por violeta cresil modificada. Através de contagem visual-manual, foram buscados dados comparativos, entre áreas cerebrais versus raça associando tipos constitucionais versus aptidão funcional. As lâminas foram analisadas com auxílio do Axióscopio Zeiss®, acoplado ao programa de análise de imagens KS-400 versão 2.0 Kontron - Zeiss®. Os fatores raças, áreas e hemisférios cerebrais podem ser variáveis dependentes entre si, pois foram encontradas diferenças estatisticamente significativas em valores correspondentes à média de corpos de neurônios das áreas estudadas nas diferentes raças, bem como entre os hemisférios cerebrais. / They had been focused in this present study three dog breeds: Boxer, Dobermann e Rottweiler, with types constitutional and aptitudes functional characteristic and between itself, being collected 4 brains of each race. Of the brians they had been removed slices of the different areas of the brain cortex, that they had been prepared second conventional histological technique and stained by modified violet cresil. Through counting appearance-manual, comparative data were reached, mainly between brain areas versus breed associating types constitutional and aptitudes functional. The slices were analyzed with aid of Axióscopio Zeiss® connected to the program of analysis of images KS-400 version 2.0 Kontron - Zeiss®. The factors races, areas and brain hemispheres can be changeable dependents between itself, therefore estatisticament significant differences in corresponding values to the average of bodies of neurons of the areas studied in the different races had been found, as well as between the brain hemispheres.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of cortical and spinal motor neurons. Animal models of ALS based on known ALS-causing mutations are instrumental in advancing our understanding of the pathophysiology of motor neuron degeneration. Recent identification of mutations in the genes encoding RNA-binding proteins TDP-43 and FUS has suggested that aberrant RNA processing may underlie common mechanisms of neurodegeneration in ALS and focused attention on the normal activities of TDP-43 and FUS. However, the role of the normal functions of RNA-binding proteins in ALS pathogenesis has not yet been established. In this thesis I present my work on novel FUS-based mouse lines aimed at clarifying the relationships between ALS-causing FUS mutations, normal FUS function and motor neuron degeneration. Experiments in mutant FUS knock-in mice show evidence of both loss- and gain-of-function effects as well as misfolding of mutant FUS protein. Characterization of mice expressing ALS-mutant human FUS cDNA in the nervous system reveals selective, early onset and slowly progressive motor neuron degeneration that is mutation dependent, involves both cell autonomous and non-cell autonomous mechanisms and models key aspects of ALS-FUS. Using a novel conditional FUS knockout mutant mouse, I also demonstrate that postnatal elimination of FUS selectively in motor neurons or more broadly in the nervous system has no effect on long-term motor neuron survival. Collectively, our findings suggest that a novel toxic function of mutant FUS, and not the loss of normal FUS function, is the primary mechanism of motor neuron degeneration in ALS-FUS.

With the recent discoveries of phenomena such as plateau potentials, bistability, and synaptic amplification the focus of motoneuron research has been directed to the dendritic processes giving rise to these latent behaviors. The common consensus is that the mechanism behind bistability (an L-type calcium channel generating a persistent inward current, PIC; Schwindt and Crill 1980, Hounsgaard and Kiehn 1985, 1989) is also responsible for the amplification of synaptic input in motoneurons. However, modeling studies utilizing only calcium-based PICs (Powers 1993, Booth et al. 1997, Elbasinouy et al. 2005) have been unable to reproduce the high degree of synaptic amplification observed in experimental preparations (Prather et al. 2001, Lee et al. 2003, Hultborn et al. 2003). The present work examines a theoretical amplification mechanism (electrotonic compression), based on a sodium PIC of dendritic origin, which acts to supplement the synaptic amplification due to the calcium PIC. The current goal is to test the "goodness-of-fit" of electrotonic compression with established mechanisms and behaviors. The findings of this modeling study support the concept of a dendritic sodium PIC which acts to reduce the attenuation of synaptic currents enroute to the motoneuron soma. Furthermore, it is suggested that the ratiometric expression of ion channels giving rise to this mechanism takes the form of a distribution "rule" applied ubiquitously across the dendritic tree, while the plateau-producing L-type calcium channels undergo a more discretized or regional distribution. This study demonstrates the power inherent to the controlled expansion of morphological complexity in an already complex model. While modeling studies are suitable testbeds for the evaluation of theoretical and/or experimentally intractable facets of physiology, great care and consideration should be given to the specification of models with high dimensionality. With the continual progression of our knowledge-base and computational capabilities, we can expect that more and more empirical observations will find their way into models of increasing complexity wherein the layers of embedded hypotheses are frequently implicit. It is therefore imperative that the neural modeling discipline adopt more rigorous methodologies to both accommodate and rein-in this growing complexity.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 89-100).

Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 3 uppsatser.

Thesis (Ph.D.)--Memorial University of Newfoundland, 2002. / Bibliography: leaves 177-206.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 8 uppsatser.

Diss. (sammanfattning) Stockholm : Karol inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol inst., 2003. / Härtill 5 uppsatser.