INTRODUÇÃO: O objetivo desta pesquisa foi medir, através da endoscopia, o plexo corióideo no forame interventricular e estruturas no assoalho do terceiro ventrículo, bem como a distância entre as artérias comunicantes posteriores e comparar essas variáveis. MÉTODOS: Estudo observacional, prospectivo realizado em 37 cérebros de cadáveres humanos adultos, de ambos os sexos, no Serviço de Verificação de Óbitos da Universidade de São Paulo, em abril de 2008, utilizando neuroendoscópio rígido. As imagens endoscópicas foram gravadas, corrigidas para distorção e mensuradas. A medida macroscópica entre as artérias comunicantes posteriores foi realizada após o estudo endoscópico. RESULTADOS: As medidas do plexo corióideo no forame interventricular, a distância látero-lateral dos corpos mamilares, a distância do recesso do infundíbulo até os corpos mamilares e do triângulo de segurança no túber cinéreo foram 1,71 mm (±0,77 mm), 2,23 mm (±0,74 mm), 3,22 mm (±0,82 mm), 3,69 mm2 (±2,09 mm2), respectivamente. O aspecto do assoalho do terceiro ventrículo e a distância interna dos corpos mamilares foi 84% opaco e 89% ausente, respectivamente. A distância média entre as artérias comunicantes posteriores foi de 12,5 mm (±2,3 mm). Associações entre translucidez do assoalho do terceiro ventrículo com as seguintes variáveis: distância láterolateral e distância interna dos corpos mamilares, assim como idade, foram identificadas. CONCLUSÕES: Até esta pesquisa, não existiam medidas sobre o plexo corióideo no forame interventricular e distância entre as artérias comunicantes posteriores na região dos corpos mamilares. As variáveis restantes, quando comparadas com a literatura, foram em maior número e em cérebros normais / INTRODUCTION: the objective of this research was to measure, through endoscopy, the interventricular foramen choroid plexus and the third ventricle floor structures, as well the distance between the communicating posterior arteries and compare these variables. METHODS: an observational, prospective study was conducted in 37 brains of adult human cadavers, of both sexes at the Death Check Unit of the University of São Paulo, in April 2008 by means of the rigid neuroendoscope. The endoscopic images were recorded, corrected for distortion and measured. The macroscopic measure between the communicating posterior arteries was performed after the endoscopic study. RESULTS: The measures of the interventricular foramen choroid plexus, the latero-lateral distance of mammillary bodies, the distance from the infundibular recess to the mammillary bodies, safety triangle in the tuber cinereum were 1.71 mm (±0.77 mm), 2.23 mm (±0.74 mm), 3.22 mm (±0.82 mm), 3.69 mm2 (±2.09 mm2), respectively. The aspect of the third ventricle floor and the internal distance of the mammillary bodies was 84% opaque and 89% absent, respectively. The mean distance between the communicating posterior arteries was 12.5 mm (±2.3 mm). Associations between the translucent floor of the third ventricle with the following variables: latero-lateral distance and internal distance of the mammillary bodies, as well as age were identified. CONCLUSIONS: Up this research, there was no account on the measures of the interventricular foramen choroid plexus and the distance between communicating posterior arteries at the level of the mammillary bodies. The remaining variables were in greater number and in normal brains, as compared with the literature

A Anatomia comparativa de mamíferos vem sendo tema de pesquisas, nas áreas biomédica e biológica com o objetivo de se buscar conhecimentos que possam auxiliar na busca sobre o entendimento do binômio unidade-variedade, dentre os símios tem sido particularmente enfocados o Babuíno e o Rhesus que, entretanto, não são próprios do Novo Mundo. O Cebus apella, animal das matas do continente Sul-americano, distribuindo-se geograficamente por quase todo o Brasil, apresenta satisfatória adaptação à vida em cativeiro condição em que, inclusive, se reproduz com facilidade. Assim, é de nosso interesse focalizar, o Cebus apella, analisando a origem, a composição e os nervos resultantes de seu plexo braquial. O objetivo imediato deste trabalho é, dar seqüência ao conhecimento de sua Anatomia, visando também o fornecimento de subsídios para interpretações anatómo-funcionais do Cebus apella, comparativamente a outros animais. O objetivo a médio e a longo prazos é o estabelecimento do padrão anatômico deste animal, culminando com a elaboração de um Atlas - texto sobre a Anatomia do macaco Cebus apella. Utilizamos 20 animais, sendo 10 machos e 10 fêmeas, adultos, pertencentes ao acervo de pesquisas da Universidade Federal de Uberlândia. A preparação das peças anatômicas foi feita segundo a metodologia usual em estudos anatômicos. Os principais nervos oriundos do plexo braquial são: supraescapular, subescapular, musculocutâneo, radial, mediano, ulnar, axilar, toracodorsal, peitoral maior e peitoral menor. Em 57% dos espécimes dissecados o plexo braquial do Cebus está constituído por raízes de C5 a T1, em 21,4% de C5 a T2, em 14,3% de C4 a T1 e em 7,3% de C4 a T2. O plano dorsal do plexo braquial contribui para a formação dos nervos: frênico, peitoral maior e peitoral menor. O plano médio origina os nervos musculocutâneo, mediano, ulnar e cutâneo medial do antebraço, enquanto o plano ventral dá origem aos nervos supraescapular, subescapular, axilar, radial e torácico longo. Discute-se a ocorrência de pré e de pós-fixação do plexo, bem como a de seu deslocamento cranial e caudal. Em conclusão o plexo braquial do Cebus apella está constituído por raízes de C5 a T1 e é organizado em um plano ventral mais simples, um médio de complexidade intermediária e um dorsal mais complexo. / Comparative Anatomy of mammals has been a relevant theme of researches in the biomedical and biological areas with the objective of looking for more information that can aid for searching on the understanding of the unit-variety complex. Among the simians, Baboon and Rhesus have been particularly focused, although they are not from the New World. The monkey Cebus apella, animal of the forests of the South American continent, being geographically distributed for almost the whole Brazil, presents satisfactory adaptation to the captive life showing a great easiness of reproduction. Thus, we intended to study the monkey Cebus apella, analyzing the origin, the composition and the resulting nerves of its brachial plexus. The immediate objective of this study was to add information to the knowledge of its Anatomy, seeking the supply of subsidies for anatomo-functional interpretations of Cebus apella comparatively to humans and domestic animals. Further, we propose to establish the anatomical pattern of this animal, culminating with the elaboration of an Atlas - text on the Anatomy of the monkey Cebus apella. Twenty adult animals, 10 male and 10 female, belonging to the collection of anatomical pieces of the Anatomy Laboratory of the Federal University of Uberlândia were obtained and prepared through fixation and dissection. The major nerves originating from the brachial plexus were: the suprascapular, the subscapular, the musculo-cutaneous, the radial, the median, the ulnar, the axillary, the thoraco-dorsal, the pectoralis major and the pectoralis minor. In the dissected specimens, the brachial plexus of Cebus apella was constituted by the roots from C5 to T1 (55,00 ± 11,12%), from C5 to T2 (25,00 ± 9,68%), from C4 to T1 (15,00 ± 7,98%) and from C4 to T2 (5,00 ± 4,87%). The ventral plan of the brachial plexus contributed for the formation of the following nerves: the phrenic, the subclavius, the pectoralis major, and the pectoralis minor. The medium plan originated the musculo-cutaneous, the median, the ulnar, and the forearm medial cutaneous nerves, while the dorsal plan originated the suprascapular, the subscapular, the axillary, the radial, thoraco-dorsal and the long thoracic nerves. In addition, the occurrence of pre- and post- fixation of the plexus as well as its cranial and caudal displacement have been discussed. In conclusion, the brachial plexus of Cebus apella constituted by the roots from C5 to T1 is organized in a simpler ventral plan, a medium plan of intermediate complexity and a more complex dorsal plan.

La grande variété de morphologie de l’appareil visuel chez les arthropodes en fait un groupe unique pour l’étude de la diversité et l'évolution du système visuel. Cependant, la plupart de nos connaissances sur le développement et l'architecture neurale du système visuel provient de quelques organismes modèles. Mon projet vise à contribuer à l'étude de la diversité et de l'évolution du système visuel des arthropodes en étudiant l'œil du crustacé Parhyale hawaiensis; axé sur son développement, sa neuro-architecture et sa fonction. En particulier, mon travail vise à caractériser la structure du système visuel, à cartographier les connexions entre les photorécepteurs (PR) et le lobe optique (LO) et à comprendre les adaptations fonctionnelles de l'œil, par rapport aux yeux des autres arthropodes.Une description de l'anatomie de base du système visuel a été réalisée au moyen de la microscopie électronique, par immunomarquage et par la production de lignées de transgénique. J'ai trouvé que Parhyale possède un œil composé de type apposition avec 8 (chez les nouveau-nés) à 50 (chez les adultes) ommatidies, chacun formée par 5 PR (R1-R5). Nous avons trouvé deux opsines, nommés Ph-Opsin1 et Ph-Opsin2, exclusivement exprimés dans la rétine. En utilisant la séquence génomique comme guide, j'ai cloné des séquences régulatrices en amont de chaque gène d’opsine et généré des rapporteurs transgéniques qui récapitulent les patterns d'expression de Ph-Opsin1 et de Ph-Opsin2. Ces rapporteurs ont révélé que R1-R4 exprime Ph-Opsin1 tandis que R5 exprime le Ph-Opsin2.Immunomarquage ainsi que l'imagerie des deux lignées transgéniques, ont montré que les PR envoient de longues projections depuis la rétine au LO. Trois neuropiles optiques ont été identifiés: la lamina, la medulla et un neuropile plus profond qui est probablement la lobula plate ou la lobula. En suivant les projections axonales des PR dans le cerveau, révélant que tous les PR se projettent dans la lamina. Ceci diffère de ce qui a été montré chez les diptères et les crustacés, où au moins un PR par ommatidie projette ses axones dans la medulla.La microscopie électronique a montré que les rhabdomères des deux paires de PR, R1 + R3 et R2 + R4, sont orthogonalement alignés les uns aux autres dans chaque ommatidie, et que le rhabdome ne tourne pas. Ces caractéristiques rendent les PR intrinsèquement sensibles aux directions spécifiques de la lumière polarisée. Par conséquent, j'ai essayé de comprendre si Parhyale réagît à la lumière polarisée, au moyen d'expériences comportementales. Les données que j'ai recueillies suggèrent que Parhyale sont phototactiques pour la lumière blanche mais ne montrent aucune réponse à la lumière polarisée dans ces essais expérimentaux. Les problèmes potentiels liés à ces tests de comportement sont discutés.Enfin, je montre que l'œil de Parhyale s'adapte rapidement à différentes conditions d'intensité lumineuse. Ceci est obtenu par le mouvement des granules de pigments, situés à l'intérieur des PR, et par des changements morphologiques de la membrane basale du PR.Ce projet est pionnier dans l'étude du système visuel chez Parhyale. C'est la première fois que des outils génétiques ont été introduits pour étudier le système visuel de crustacés. Il établit Parhyale comme un puissant système expérimental pour des études in vivo de développement des yeux composé et de ciblage axonal du système visuel, un champ actuellement dominé par des études sur une seule espèce de mouche. / The wide diversity of eye designs present in arthropods makes them a unique group for studying the diversity and evolution of the visual system. However, most of our knowledge on the development and the neural architecture of the visual system comes from few model organisms. My project aims to contribute to the study of the diversity and evolution of the arthropod visual system by studying the eye of the crustacean Parhyale hawaiensis; focusing on its development, neuroarchitecture and function. In particular, my work aims to characterize the structure of the visual system, to map the connections between photoreceptors (PR) and optic lobe (OL) and to understand the functional adaptations of the eye, in relation to the eyes of other arthropods.A description of the basic anatomy of the visual system was performed by means of electron microscopy, immunostainings and by generating transgenic reporter lines. I found that Parhyale has an apposition-type compound eye with 8 (in hatchlings) to 50 (in adults) ommatidia, each one formed by 5 PR cells (R1-R5).Two opsins were found in Parhyale, named Ph-Opsin1 and Ph-Opsin2, which are exclusively expressed in the retina. Using the genome sequence as a guide, I cloned upstream regulatory sequences from each opsin genes and generated transgenic reporters that recapitulate the expression patterns of Ph-Opsin1 and Ph-Opsin2. These reporters revealed that R1-R4 express Ph-Opsin1 while R5 expresses Ph-Opsin2.Immunostainings and live imaging of the two transgenic lines showed that PR cells send long projections from the retina to the OL, via an optic nerve. Three optic neuropils were identified: lamina, medulla and a deeper neuropil, possibly the lobula or lobula plate. Following the axonal projections of the PR into the brain, revealed that all PR project to the lamina. This differs from what has been shown in dipterans and crustaceans, where at least one PR per ommatidium projects to the medulla. Electron microscopy showed that the rhabdomeres of two pairs of PR, R1+R3 and R2+R4, are orthogonally aligned to each other in each ommatidium, and that the rhabdom does not rotate. These features render the PR intrinsically sensitive to specific directions of light polarisation. Therefore, I tried to understand whether and how Parhyale respond to polarised light. I developed two experimental setups to address whether Parhyale shows behavioural responses triggered by light polarisation. The data I have collected suggest that Parhyale are phototactic to dim white light but show no response to polarised light in these specific experimental assays. Potential problems with these behavioural assays are discussed.Finally I show that the eye of Parhyale quickly adapts to different conditions of light intensity. This is achieved by movement of the shielding pigment granules, located inside the PR cells and by morphological changes of the PR basal membrane.This project is pioneering the study of the visual system in Parhyale. It is the first time that genetic tools have been introduced to study the crustacean visual system. It establishes Parhyale as a powerful experimental system for in vivo studies of compound eye development and axonal targeting, a field currently dominated by studies in a single species of fruitfly.

La dyslexie développementale est un trouble spécifique de l'apprentissage de la lecture qui affecte 3 à 7% des enfants d'âge scolaire. Il est bien établi aujourd'hui que la dyslexie découle en partie de variations génétiques qui causent des changements lors du développement cérébral, qui, à leur tour, ont des conséquences au niveau cognitif. Cette thèse s'appuie sur les analyses morphométriques de trois des sillons principaux du cerveau dans trois grands ensembles de données d'imagerie par résonance magnétique : 102 participants français, 80 participants polonais et 70 participants allemands, avec, dans chaque jeu de données, environ la moitié de participants ayant été diagnostiqués dyslexiques et la moitié de lecteurs normaux. J'ai étudié le sillon central, la scissure Sylvienne et le sillon temporal supérieur grâce aux outils de labellisation automatique et de mesures du logiciel BrainVISA. J'ai mesuré des propriétés quantitatives (surface et profondeur) ainsi que des propriétés qualitatives (configuration) de chaque sillon. J'ai montré une triple interaction entre groupe, sexe et hémisphère dans la profondeur moyenne du sillon central, laissant penser que les participants contrôles et dyslexiques diffèrent en terme d'asymétrie de profondeur de ce sillon. Comme la sulcation est un processus se déroulant de façon précoce lors du développement du cerveau et qui semble moins plastique que d'autres mesures cérébrales (comme, par exemple, les volumes de matière grise), ce résultat pourrait s'avérer être un marqueur précoce du risque de dyslexie plutôt que la conséquence de mauvaises capacités de lecture. / Developmental dyslexia is a specific disorder of reading acquisition that affects 3 to 7% of school-aged children. It is well established that dyslexia is partly caused by genetic variations whitch cause changes in brain development, whitch then have consequences at the cognitive level. This Ph.D thesis is based on morphometry analysis of three main sulci of the brain in three large databases of brain magnetic resonance images: 102 participants from France, 80 particpants from Poland and 70 participants from Germany, with, in each database, about half of participants were diagnosed with dyslexia and half of normal readers. I have studied the central sulcus, the Sylvian fissure and the superior temporal sulcus thanks to the automatic labelisation and measures tools in the BrainVISA software. I have measured some quantitative properties (surface and depth) as well as some qualitative ones (configuration) of each sulcus. I have shown a triple interaction between group, sex and hemisphere in the mean depth of the central sulcus. This result allows us to think that control and dyslexic participants may be different in terms of depth asymetry in this particular sulcus. Given that sulcation is an early process during brain development et that it seems to be less plastic than other brain measures (like, for example, grey matter volumes), this result may be an early marker of risk factors for dyslexia rather than a consequence of poor reading.

The circadian timing system establishes daily rhythms in behavior and physiology throughout the body, ensuring that functions like activity, sleep and hormone release are appropriately timed. Research suggests that his temporal synchrony within the body is quite important for health and survival. In mammals, the central circadian pacemaker in the suprachiasmatic nucleus (SCN) drives rhythms in behavior and physiology in large part by stimulating or inhibiting other brain regions responsible for these functions at the appropriate times of day. This timed signal is often indirect, i.e. relayed or possibly processed through a series of neurons in different brain regions before reaching the effector site. The subparaventricular zone (SPZ), a region adjacent to the SCN which is the main recipient of direct neuronal inputs from the SCN, is thought to be a critical relay for SCN signals, since loss of the SPZ results in loss of circadian rhythms in body temperature, activity and sleep/wakefulness. Another important relay site, the dorsomedial hypothalamic nucleus (DMH) gets direct input from both the SCN and SPZ and is critical for normal expression of various circadian rhythms.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a profound loss of dopaminergic neurons from the substantia nigra (SN). Among the many pathogenic mechanisms thought to be responsible for the demise of these cells, dopamine (DA)-dependent oxidative stress and oxidative damage has taken center stage due to extensive experimental evidence showing that DA-derived reactive oxygen species (ROS) and oxidized DA metabolites are toxic to SN neurons. Despite its being the most efficacious drug for symptom reversal in PD, there is concern that levodopa (LD) may contribute to the neuronal degeneration and progression of PD by enhancing DA concentrations and turnover in surviving dopaminergic neurons. The present study investigates the potential neurotoxic and neuroprotective effects of DA in vitro. These effects are compared to the toxicity and neuroprotective effects observed in the rat striatum after the administration of LD and selegiline (SEL), both of which increase striatal DA levels. The effects of exogenous LD and/or SEL administration on both the oxidative stress caused by increased striatal iron (II) levels and its consequences have also been investigated. 6-Hydroxydopamine (6-OHDA) is a potent neurotoxin used to mimic dopaminergic degeneration in animal models of PD. The formation of 6-OHDA in vivo could destroy central dopaminergic nerve terminals and enhance the progression of PD. Inorganic studies using high performance liquid chromatography with electrochemical detection (HPLC-ECD) show that hydroxyl radicals can react with DA to form 6-OHDA in vitro. SEL results in a significant decrease in the formation of 6-OHDA in vitro, probably as a result of its antioxidant properties. However, the exogenous administration of LD, with or without SEL, either does not lead to the formation of striatal 6-OHDA in vivo or produces concentrations below the detection limit of the assay. This is despite the fact that striatal DA levels in these rats are significantly elevated (two-fold) compared to the control group. The auto-oxidation and monoamine oxidase (MAO)-mediated metabolism of DA causes an increase in the production of superoxide anions in whole rat brain homogenate in vitro. In addition to this, DA is able to enhance the production of hydroxyl radicals by Fenton chemistry (Fe(III)-EDTA/H2O2) in a cell free environment. Treatment with systemic LD elevates the production of striatal superoxide anions, but does not lead to a detectable increase in striatal hydroxyl radical production in vivo. The co-adminstration of SEL with LD is able to prevent the LD induced rise in striatal superoxide levels. It has been found that the presence of DA or 6-OHDA is able to reduce lipid peroxidation in whole rat brain homogenate induced by Fe(II)-EDTA/H2O2 and ascorbate (Fenton system). However, DA and 6-OHDA increase protein oxidation in rat brain homogenate, which is further increased in the presence of the Fenton system. In addition to this, the incubation of rat brain homogenate with DA or 6-OHDA is also accompanied by a significant reduction in the total GSH content of the homogenate. The exogenous administration of LD and/or SEL was found to have no detrimental effects on striatal lipids, proteins or total GSH levels. Systemic LD administration actually had a neuroprotective effect in the striatum by inhibiting iron (II) induced lipid peroxidation. Inorganic studies, including electrochemistry and the ferrozine assay show that DA and 6-OHDA are able to release iron from ferritin, as iron (II), and that DA can bind iron (III), a fact that may easily impede the availability of this metal ion for participation in the Fenton reaction. The binding of iron (III) by DA appears to discard the involvement of the Fenton reaction in the increased production of hydroxyl radicals induced by the addition of DA to mixtures containing Fe(II)-EDTA and hydrogen peroxide. 6-OHDA did not form a metal-ligand complex with iron (II) or iron (III). In addition to the antioxidant activity and MAO-B inhibitory activity of SEL, the iron binding studies show that SEL has weak iron (II) chelating activity and that it can also form complexes with iron (III). This may therefore be another mechanism involved in the neuroprotective action of SEL. The results of the pineal indole metabolism study show that the systemic administration of SEL increases the production of N-acetylserotonin (NAS) by the pineal gland. NAS has been demonstrated to be a potent antioxidant in the brain and protects against 6-OHDA induced toxicity. The results of this study show that DA displays antioxidant properties in relation to lipid eroxidation and exhibits pro-oxidant properties by causing an increase in the production of hydroxyl radicals and superoxide anions, as well as protein oxidation and a loss of total GSH content. Despite the toxic effects of DA in vitro, the treatment of rats with exogenous LD does not cause oxidative stress or oxidative damage. The results also show that LD and SEL have some neuroprotective properties which make these agents useful in the treatment of PD.

Uremic pruritus (UP) arises in end-stage renal disease (ESRD) and is not relieved by proper dialysis. While the pathogenesis of UP is not well understood, UP responds poorly to anti-histamines. We performed a case-control study to test if cutaneous protease-mediated, non-histamine itch is augmented in UP, and if UP is associated with altered epidermal and/or papillary dermal innervation. We recruited 12 hemodialysis subjects with ESRD-specific itch (cases) (Visual Analogue Scale (VAS)-average itch in the preceding week, 78/100), and 13 age- and sex-matched hemodialysis subjects without pruritus (controls) (VAS- average itch in the preceding week, 0/100; p<0.0001 cases vs. controls). Cowhage spicule-induced itch was induced in the back where all subjects exhibited itch, and the entire duration of itch was measured with the general Labeled Magnitude Scale. Subsequently, a punch biopsy was taken from this sensory-tested skin and multi-label immunohistochemistry was performed to measure epidermal and papillary dermal innervation. In cases vs. controls, cowhage-induced area under the curve (AUC) for itch was significantly larger (median, 25%–75%: 175.4, 101.0–252.2 vs. 42.4, 24.0–160; p=0.04) as was perceived peak itch intensity (53.6, 53.3–78.9 vs. 34.2, 20.9–55.6; p=0.02). Cases showed a significant reduction in papillary dermal nerve length (PDNL)/mm epidermis (2295, 1659–2970 vs. 2909, 2228–3523; p=0.003), resulting from the loss of papillary dermal (PD)-calcitonin gene related peptide (CGRP) (+) nerves (p<0.0001), with preservation of %PD-substance P (+) nerves (p=0.1) and intraepidermal nerve fiber density (p=0.1). VAS-average itch in the preceding week negatively correlated with PDNL/mm epidermis (correlation coefficient (CC)=-0.53, p=0.003) and %PD-CGRP (+) nerves (CC=-0.37, p=0.03). Cowhage-induced AUC-itch negatively correlated with %PD-CGRP nerves only in cases (CC=-0.40, p=0.02). Our data suggest augmented protease-dependent signaling contributes to UP and indicate a mechanism for how PD-CGRP (+) nerve loss contributes to UP and augmented cowhage-itch: loss of an afferent skin-derived itch-inhibition signal to the spinal cord dorsal horn. / 2016-10-02T00:00:00Z

No description available.

付記する学位プログラム名: 京都大学卓越大学院プログラム「メディカルイノベーション大学院プログラム」 / 京都大学 / 新制・課程博士 / 博士(医学) / 甲第25191号 / 医博第5077号 / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邉 大, 教授 林 康紀, 教授 高橋 淳 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Dissertation (PhD)--Stellenbosch University, 2001. / ENGLISH ABSTRACT: Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts (obsessions) and repetiti ve mental acts or behaviours (compulsions) . For many years, it was considered a rather uncommon condition, caused by unconscious conflict, and somewhat resistant to treatment. In recent decades, however, it has emerged that OCD is a highly prevalent disorder, mediated by particular neuroanatomical circuits (e.g. striatal pathways) and neurochemical systems (e.g. the serotonin system), and responsive to treatment with serotonin reuptake inhibitors (SRIs) . Nevertheless, many questions remain; about the specificity of neuroanatomical findings to OCD, about the role of the multiple serotonin (5-HT) receptor subtypes (e.g. 5-HT10)' and about the appropriate pharmacotherapy for patients resistent to SRI treatment? In a series of studies, 1) the neuroanatomy of OCD was assessed by means of magnetic resonance imaging and neuropsychological testing, 2) the neurochemistry of OCD was assessed by means of functional brain imaging after administration of a 5-HT10 agonist, and 3) the pharmacotherapy of OCD was explored in a series of treatment-refractory OCD and OCD spectrum disorder patients using SRI augmentation with a dopamine blocker. Although no significant difference was found in the volume of the caudate in women with OCD and controls, there was a significant correlation between caudate volume and neuropsychological dysfunction in patients, consistent with evidence of striatal involvement in OCD. Functional imaging demonstrated behavioural heterogeneity, but brain-behaviour correlations were positive, consistent with preclinical evidence of a role for the 5-HTlD receptor in the mediation of OCD. Finally, preliminary treatment findings with dopamine blocker augmentation of a SRI were promising, consistent with preclinical understandings of the interactions between the dopamine and serotonin systems. Although oeD is a complex disorder, a number of future research avenues hold promise for providing a thorough delineation of its pathogenesis. / AFRIKAANSE OPSOMMING: Obsessief-kompulsiewe steuring (OKS) word gekenmerk deur indringende gedagtes (obsessies) en herhalende gedagtes of gedrag (kompulsies). Vir baie jare is dit beskou as 'n redelik seldsame toestand wat veroorsaak word deur onbewustelike konflik, en wat in 'n mate teen behandeling weerstandig is. Meer onlangs het dit egter na vore getree as 'n toestand wat baie dikwels voorkom, wat deur spesifieke neuroanatomiese siklusse (bv. striatale bane) en neurochemiese sisteme (bv. die serotonien-sisteem) teweeg gebring word, en wat op behandeling met serotonien heropname inhibeerders (SHIs) reageer. Nogtans is daar steeds baie vrae; oor die spesifisiteit van neuroanatomiese bevindinge vir OKS, oor die rol van die veelvuldige serotonien (5-HT) reseptor subtipes (bv. 5- HT1D), en oor die toepaslike farmakoterapie vir pasiënte wat weerstandig is vir SHI behandeling. In' n reeks van navorsingstudies, is 1.) die neuroanatomie van OKS deur middel van magnetiese resonans beelding en neurosielkundige toetse ondersoek, 2. ) die neurochemie van OKS deur middel van funksionele breinbeelding na toediening van 'n 5-HT1D agonis bepaal, en 3.) die farmakoterapie van OKS in 'n reeks van behandelingsweerstandige OKS en OKS-spektrum steuring pasiënte - waar gebruik gemaak is van SHI aanvulling met 'n dopamien-blokker - ondersoek. Alhoewel daar geen beduidende verskil in die volume van die caudata in vroue met OKS en kontroles gevind is nie, was daar 'n beduidende korrelasie tussen die caudata volume en neurosielkundige wanfunksionering in pasiënte, in ooreenstemming met striatale betrokkenheid in OKS. Funksionele beelding het positief, in demonstreer, maar ooreenstemming met brein-gedrag pre-kliniese heterogeneïteit korrelasies was in gedrag bewyse vir 'n rol vir die 5-HT1D reseptor in die bemiddeling van OKS. Ten laaste, voorlopige behandelingsbevindinge oor dopamienblokker aanvulling van 'n SHI is belowend, in ooreenstemming met v