Die hier vorliegenden klinischen und experimentellen Arbeiten hatten zum Ziel apoptotische Mechanismen einer Schädigung des unreifen zentralen Nervensystems näher zu charakterisieren. Im tierexperimentellen Teil der Studien wurden apoptotische Faktoren und deren Regulation an zwei unterschiedlichen experimentellen Schädigungsmodellen des unreifen Gehirns (Hypoxie, Trauma) untersucht, mit dem Ziel mögliche neuroprotektive Ansätze zu identifizieren. In einem weiteren Teil der Arbeiten ging es darum, die Darstellung der Hirnschädigung von sehr unreifer Frühgeborenen in der Magnetresonanztomographie (MRT) histologisch an Autopsiematerial zu vergleichen. An Autopsiefällen mit pontosubikulärer Nekrose (PSN) wurde die Bedeutung der pro-apoptotischen Marker CD95/Fas/Fas Ligand bei einer Hypoxie erarbeitet. Der klinische Teil der Untersuchungen hatte die Identifizierung Apoptose-regulierender Faktoren (lösliche Form von Fas/Fas Ligand, Caspase 3) im Liquor von Patienten mit Hydrozephalus zum Ziel. Die in dieser kumulativen Habilitationsschrift aufgeführten Arbeiten haben die weitreichende Rolle apoptotischer Mechanismen, insbesondere des Zelloberflächenrezeptors CD95/Fas, in unterschiedlichen klinischen und experimentellen Schädigungsmodellen des unreifen Gehirns demonstriert und weiterführende Fragestellungen aufgezeigt. Im klinischen Umfeld besteht mit neueren bildgebenden Verfahren und der Untersuchung löslicher apoptotischer Marker die Möglichkeit, Schädigungen des Gehirns näher zu charakterisieren. Mit diesen Untersuchungen wurden zudem Grundlagen zur Identifikation möglicher neuroprotektiver Angriffspunkte erarbeitet. / The studies presented here aimed at the investigation of apoptotic mechanisms in the context of damage to the immature central nervous system. The expression and regulation of apoptotic factors was demonstrated in two experimental animal models of damage to the immature brain (hypoxia, trauma), in order to identify possible neuroprotective strategies. The aim of an additional study was to compare the magnetic resonance imaging (MRI) appearances of the immature brain with neuropathological findings at post-mortem examination. In human autopsy material consisting of cases with pontosubicular necrosis (PSN) the expression of pro-apoptotic markers (CD95/Fas/Fas ligand) was demonstrated. The clinical part of the projected investigations identified apoptosis-regulating elements (soluble Fas /Fas ligand, Caspase-3) in the cerebrospinal fluid (CSF) of children with hydrocephalus. The clinical and experimental studies confirmed the importance of apoptotic mechanisms in the pathophysiology of neurodegeneration in the immature brain. In a clinical setting new MRI imaging procedures and identification of novel biochemical markers have the potential to further characterize damage processes. The investigations presented here identified molecular targets for possible neuroprotective therapies.

No description available.

Les cellules souches neurales adultes (aNSCs) sont définies par des fonctions d’auto-Renouvellement et de multipotence qui leur permettent de générer dans le cerveau adulte tant des neurones que des cellules gliales. Contrairement aux mammifères, le cerveau de poisson zèbre présente de nombreuses zones de neurogenèse adulte dont la plus caractérisée est la zone ventriculaire du pallium. Elle est composée de cellules de glies radiaires qui font office de aNSCs dans cette partie du cerveau. Quels progéniteurs neuraux embryonnaires sont sélectionnés pour être à l’origine de ces aNSCs reste mal connu. Ce travail a pour objectif de déterminer la contribution relative de deux populations de progéniteurs neuraux embryonnaires, les “clusters proneuraux” (impliqués dans la neurogenèse embryonnaire) et les “pools de progéniteurs” (caractérisés par une neurogenèse tardive), dans la formation des aNSCs du pallium de poisson zèbre. Dans un premier temps, à l’aide de techniques génétiques de lignage cellulaire, nous avons pu identifier la population de progéniteurs neuraux embryonnaires à l’origine d’une sous-Population des aNSCs située dans la partie dorso-Médiane du pallium. Des expériences de lignage utilisant la lignée de poisson zèbre her4:ERT2CreERT2 combinées à des traitements inhibiteurs de la voie de signalisation Notch nous ont permis de déterminer que les progéniteurs neuraux donnant naissance aux aNSCs du pallium dorso-Médian expriment le gène « Enhancer of split » her4, qui caractérise les “clusters proneuraux”, ce dès des stades très précoces du développement. Dans un second temps, des analyses clonales ainsi que des recombinaisons spatialement contrôlées par laser nous ont permis de mettre en évidence que les aNSCs de la partie latérale du pallium de poisson zèbre ne proviennent pas de progéniteurs embryonnaires exprimant her4 et maintenus par la voie Notch, mais d’une population restreinte de cellules neuroépitheliales situées dans la plaque du toit du télencéphale embryonnaire. Ces cellules présentent des caractéristiques spécifiques des “pool de progéniteurs”, à savoir l’expression de gènes her non-Canoniques (dont l’expression n’est pas dépendante de la voie de signalisation Notch) tels que her6 et her9, l’expression de ligands de voies de signalisation telles que Wnt, BMP et FGF, et une neurogenèse tardive. Elles génèrent progressivement, à partir du stade juvénile, une grande partie des aNSCs du pallium latéral. De plus, une partie de ces cellules neuroépitheliales persistent dans le pallium latéral postérieur chez l’adulte et continuent de former de novo des aNSCs dans cette région du cerveau. Outre la vision globale que cette étude nous a permis d’avoir sur l’origine embryonnaire de la totalité des aNSCs du pallium de poisson zèbre, elle a aussi délivré des informations sur les étapes de maturation progressive des progéniteurs embryonnaires pour former les aNSCs, et les similitudes et divergences qui existent entre la population dorso-Médiane et latérale à ce sujet. Enfin, en traçant les neurones issus des cellules souches à différents stades, cette étude a pour la première fois mis en évidence la formation progressive des compartiments neuronaux du pallium de poisson zèbre, et ainsi permis d’apprécier les homologies de ces compartiments avec les régions du pallium de souris. / Adult neural stem cells (aNSCs) are defined by their self-Renewal and multipotency, which allow them to generate both neurons and glial cells in the adult brain. Contrary to mammals, the zebrafish brain maintains numerous neurogenic zones in the adult, among which the most characterized is the pallial ventricular zone. It is composed of radial glial cells serving as aNSCs. Which embryonic neural progenitors are at the origin of these aNSCs is still unknown. This work aims to determine the relative contributions of two embryonic neural progenitor populations, the «proneural clusters» (involved in embryonic neurogenesis) and the « progenitor pools » (characterized by a delayed neurogenesis), to the formation of aNSCs in the zebrafish pallium. First, using genetic lineage tracing techniques, we were able to identify the embryonic neural progenitor population at the origin of a subpopulation of aNSCs located in the dorso-Medial part of the pallium. The her4:ERT2CreERT2 transgenic driver line, combined with pharmacological treatments inhibiting the Notch signalling pathway, allowed showing that neural progenitors giving rise to dorso-Medial pallial aNSCs express the « Enhancer of split » her4 gene, specifically expressed in « proneural clusters » from very early stages of development. As a second step, clonal analyses as well as spatially controlled recombinations by laser highlighted that aNSCs of the zebrafish lateral pallium do not derive from her4-Positive embryonic progenitors maintained by the Notch pathway, but from a restricted population of neuroepithelial cells located in the embryonic telencephalic roof plate. These cells display « progenitor pool » specific features, as for instance the expression of non-Canonical her genes (independent of Notch signalling) such as her6 and her9, the expression of components of signalling pathways such as Wnt, BMP, FGF, and a late neurogenesis onset. These progenitors progressively generate, from juvenile stages, the vast majority of the aNSCs of the lateral pallium. Most interestingly, a small population of these neuroepithelial cells persists in the postero-Lateral pallium at adult stage and keeps generating de novo aNSCs of this brain region. In addition to identifying the origin of pallial aNSCs in the zebrafish, this study also delivers information on the progressive maturation steps that embryonic progenitors undergo to generate aNSCs, and highlights similarities and differencies existing between the dorso-Medial and lateral progenitors. Finally, this work also permits tracing the neurons generated by stem cells at different stages. This reveals for the first time the progressive formation of the different zebrafish pallial compartements, and allows appreciating their homologies with the mouse pallial regions.

The novel manuscript Girl in the Shadows tells the story of two teenage girls whose friendship, safety and sanity are pushed to the limits when an unexplained phenomenon invades their lives. Sixteen-year-old Tash has everything a teenage girl could want: good looks, brains and freedom from her busy parents. But when she looks into her mirror, a stranger’s face stares back at her. Her best friend Mal believes it’s an evil spirit and enters the world of the supernatural to find answers. But spell books and ouija boards cannot fix a problem that comes from deep within the soul. It will take a journey to the edge of madness for Tash to face the truth inside her heart and see the evil that lurks in her home. And Mal’s love and courage to pull her back into life. The exegesis examines resilience and coping strategies in adolescence, in particular, the relationship of trauma to brain development in children and teenagers. It draws on recent discoveries in neuroscience and psychology to provide a framework to examine the role of coping strategies in building resilience. Within this broader context, it analyses two works of contemporary young adult fiction, Freaky Green Eyes by Joyce Carol Oates and Sonya Hartnett’s Surrender, their use of the split persona as a coping mechanism within young adult fiction and the potential of young adult literature as a tool to help build resilience in teen readers.

As fases da pré-adolescência e adolescência são complexas porque englobam diversas mudanças nos indivíduos, se passa por rápido crescimento físico, alteração hormonal, mudanças no ambiente social e nas exigências. Estas fases são caracterizadas por comportamentos de risco por falta de controle inibitório, que está relacionado ao córtex pré- frontal, última área a se desenvolver do sistema nervoso. Há também a experimentação de álcool e drogas durante a adolescência e puberdade. Este trabalho realizou três estudos que abrangeram a temática do controle inibitório na pré-adolescência e adolescência. O primeiro foi uma revisão sistemática a respeito da avaliação do controle inibitório na adolescência e uso de neuroimagem. O segundo investigou a relação do consumo de álcool na adolescência com uso excessivo de bebidas alcóolicas dos pais. E o terceiro objetivou avaliar a impulsividade, controle inibitório e consumo de álcool em indivíduos de 10 a 16 anos. Os três artigos sugeriram um padrão de maior controle inibitório ao longo do desenvolvimento na fase da adolescência. Ainda foi possível observar que as bebidas alcóolicas têm sido consumidas cada vez mais precocemente e em maiores quantidades. Além disso, o consumo excessivo de álcool dos pais de adolescentes pode influenciar no consumo dos filhos nesta fase. / Stages of pre-adolescence and adolescence are complex because they involve several changes in individuals, they pass through a fast physical growth, hormonal changes, changes in the social environment and the requirements. These phases are characterized by risk behavior for lack of inhibitory control, which is related to the prefrontal cortex, the last area to develop the nervous system. There are also experimenting with alcohol and drugs during adolescence and puberty. This work conducted three studies which approached the inhibitory control in preadolescence and adolescence. The first was a systematic review regarding the inhibitory control assessment in adolescence and use of neuroimaging. The second investigated the relationship of alcohol consumption in adolescence with excessive use of alcohol from parents. And the third was aimed at evaluating impulsivity, inhibitory control and alcohol consumption in individuals 10-16 years. The three articles suggested a pattern of greater inhibitory control over development in adolescence. Although it was observed that the alcoholic beverages have been consumed ever earlier and in larger quantities. In addition, excessive alcohol consumption of parents of teenagers can influence the consumption of children at this stage.

As fases da pré-adolescência e adolescência são complexas porque englobam diversas mudanças nos indivíduos, se passa por rápido crescimento físico, alteração hormonal, mudanças no ambiente social e nas exigências. Estas fases são caracterizadas por comportamentos de risco por falta de controle inibitório, que está relacionado ao córtex pré- frontal, última área a se desenvolver do sistema nervoso. Há também a experimentação de álcool e drogas durante a adolescência e puberdade. Este trabalho realizou três estudos que abrangeram a temática do controle inibitório na pré-adolescência e adolescência. O primeiro foi uma revisão sistemática a respeito da avaliação do controle inibitório na adolescência e uso de neuroimagem. O segundo investigou a relação do consumo de álcool na adolescência com uso excessivo de bebidas alcóolicas dos pais. E o terceiro objetivou avaliar a impulsividade, controle inibitório e consumo de álcool em indivíduos de 10 a 16 anos. Os três artigos sugeriram um padrão de maior controle inibitório ao longo do desenvolvimento na fase da adolescência. Ainda foi possível observar que as bebidas alcóolicas têm sido consumidas cada vez mais precocemente e em maiores quantidades. Além disso, o consumo excessivo de álcool dos pais de adolescentes pode influenciar no consumo dos filhos nesta fase. / Stages of pre-adolescence and adolescence are complex because they involve several changes in individuals, they pass through a fast physical growth, hormonal changes, changes in the social environment and the requirements. These phases are characterized by risk behavior for lack of inhibitory control, which is related to the prefrontal cortex, the last area to develop the nervous system. There are also experimenting with alcohol and drugs during adolescence and puberty. This work conducted three studies which approached the inhibitory control in preadolescence and adolescence. The first was a systematic review regarding the inhibitory control assessment in adolescence and use of neuroimaging. The second investigated the relationship of alcohol consumption in adolescence with excessive use of alcohol from parents. And the third was aimed at evaluating impulsivity, inhibitory control and alcohol consumption in individuals 10-16 years. The three articles suggested a pattern of greater inhibitory control over development in adolescence. Although it was observed that the alcoholic beverages have been consumed ever earlier and in larger quantities. In addition, excessive alcohol consumption of parents of teenagers can influence the consumption of children at this stage.

As fases da pré-adolescência e adolescência são complexas porque englobam diversas mudanças nos indivíduos, se passa por rápido crescimento físico, alteração hormonal, mudanças no ambiente social e nas exigências. Estas fases são caracterizadas por comportamentos de risco por falta de controle inibitório, que está relacionado ao córtex pré- frontal, última área a se desenvolver do sistema nervoso. Há também a experimentação de álcool e drogas durante a adolescência e puberdade. Este trabalho realizou três estudos que abrangeram a temática do controle inibitório na pré-adolescência e adolescência. O primeiro foi uma revisão sistemática a respeito da avaliação do controle inibitório na adolescência e uso de neuroimagem. O segundo investigou a relação do consumo de álcool na adolescência com uso excessivo de bebidas alcóolicas dos pais. E o terceiro objetivou avaliar a impulsividade, controle inibitório e consumo de álcool em indivíduos de 10 a 16 anos. Os três artigos sugeriram um padrão de maior controle inibitório ao longo do desenvolvimento na fase da adolescência. Ainda foi possível observar que as bebidas alcóolicas têm sido consumidas cada vez mais precocemente e em maiores quantidades. Além disso, o consumo excessivo de álcool dos pais de adolescentes pode influenciar no consumo dos filhos nesta fase. / Stages of pre-adolescence and adolescence are complex because they involve several changes in individuals, they pass through a fast physical growth, hormonal changes, changes in the social environment and the requirements. These phases are characterized by risk behavior for lack of inhibitory control, which is related to the prefrontal cortex, the last area to develop the nervous system. There are also experimenting with alcohol and drugs during adolescence and puberty. This work conducted three studies which approached the inhibitory control in preadolescence and adolescence. The first was a systematic review regarding the inhibitory control assessment in adolescence and use of neuroimaging. The second investigated the relationship of alcohol consumption in adolescence with excessive use of alcohol from parents. And the third was aimed at evaluating impulsivity, inhibitory control and alcohol consumption in individuals 10-16 years. The three articles suggested a pattern of greater inhibitory control over development in adolescence. Although it was observed that the alcoholic beverages have been consumed ever earlier and in larger quantities. In addition, excessive alcohol consumption of parents of teenagers can influence the consumption of children at this stage.

Submitted by Irene Nascimento (irene.kessia@ufpe.br) on 2016-07-29T17:41:36Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese de doutorado Noranege.pdf: 2102537 bytes, checksum: 369a984689437961ceddacbe025eaf15 (MD5) / Made available in DSpace on 2016-07-29T17:41:36Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese de doutorado Noranege.pdf: 2102537 bytes, checksum: 369a984689437961ceddacbe025eaf15 (MD5) Previous issue date: 2016-02-25 / Facepe / Há evidências clínicas e experimentais de que os hormônios ovarianos exercem profundas e duradouras ações sobre o cérebro, tanto durante o seu desenvolvimento, quanto após essa fase (cérebro adulto). Algumas dessas ações repercutem de forma importante sobre a excitabilidade cerebral. Em trabalho anterior, filhotes de ratas Wistar aos 7 dias pós-natais foram submetidas à ovariectomia bilateral (grupo ovx) ou pseudo-cirurgia de ovariectomia (grupo sham) ou nenhuma cirurgia (grupo ingênuo). Quando os filhotes alcançaram a idade adulta (90-120 dias) o grupo ovx e os dois grupos controles (sham e ingênuo-na fase proestro) foram submetidos ao registro da Depressão Alastrante Cortical (DAC), fenômeno que é influenciado pela excitabilidade do cérebro. No grupo ovx, a DAC se propagou com velocidades significativamente menores em comparação aos dois grupos controle. Neste trabalho continuou-se essa linha de investigação. Inicialmente, demonstrou-se que a ovariectomia na vida adulta não se acompanha dos efeitos, observados em ratas com ovariectomia precoce. Esses dados, juntados àqueles obtidos durante o mestrado, originaram um artigo publicado na revista “International Journal of Developmental Neuroscience”. Em seguida, estudou-se os efeitos, sobre a DAC, da interação entre a administração de hormônios ovarianos e condições desfavoráveis de lactação (amamentação em ninhadas de grande tamanho). Ratas Wistar foram tratadas com estradiol ou progesterona ou ambos dos 7 aos 21 dias de vida ou submetidas, na vida adulta, a aplicações tópicas, no córtex cerebral, de diferentes concentrações de estradiol ou progesterona durante o registro da DAC. Ao contrário do observado anteriormente em ratas ovariectomizadas, o tratamento sistêmico ou tópico com ambos os hormônios acelerou a propagação da DAC, em comparação com ratas controle, tratadas com o veículo. No caso da aplicação tópica, o efeito apresentou-se reversível e dependente da dose aplicada. Sugere-se que tais efeitos estão relacionados com a açzão dos hormônios ovarianos sobre a excitabilidade cerebral. / There is experimental and clinical evidence that ovarian hormones exert profound and lasting action on the brain, both during its development, and after this phase (adult brain). Some of these actions have repercussions significantly on brain excitability. In previous work, offspring of female rats at 7 postnatal days were subjected to bilateral ovariectomy (OVX group) or ovariectomy pseudo- surgery (sham group) or no surgery (naive group). When the pups reached adulthood (90-120 days) the OVX group and the two control groups (sham and naive in the proestrus phase) were subjected to the recording of Cortical Spreading Depression (CSD), a phenomenon that is influenced by the excitability of the brain. In the OVX group, the CSD spread with significantly lower rates compared to the two control group.it was demonstrated that ovariectomy in the period of brain development reduced the spread of cortical spreading depression (CSD), a phenomenon which is influenced by brain excitability. This work continued this line of research. Initially, it was demonstrated that ovariectomy in adult life is not accompanied by the effects observed in rats with early ovariectomy. These data, coupled to those obtained during the master, gave an article published in the "International Journal of Developmental Neuroscience" journal. Then studied the effects on the CSD, the interaction between the administration of ovarian hormones and unfavorable conditions of lactation (suckling in large litters). Wistar rats were treated with estradiol or progesterone or both from 7 to 21 days or submitted in adult life, topical applications, the cerebral cortex, different concentrations of estradiol or progesterone during registration of CSD. Unlike the previously observed in ovariectomized rats, the systemic or topical treatment with both hormones accelerated the velocity of the CSD compared to control rats treated with the vehicle. In the case of topical application, the effect is reversible and showed dependent on the applied dose. It is suggested that these effects are related to the action of ovarian hormones on brain excitability.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-12-01T12:36:12Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO_SUÊNIA_RG.pdf: 2120319 bytes, checksum: 3282857c01e879a00796958f4df66f2f (MD5) / Made available in DSpace on 2016-12-01T12:36:12Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO_SUÊNIA_RG.pdf: 2120319 bytes, checksum: 3282857c01e879a00796958f4df66f2f (MD5) Previous issue date: 2016-02-19 / CNPq / Glutamato monossódico (MSG) é um aminoácido neuroexcitatório utilizado como reforçador do sabor dos alimentos. Está envolvido em diversos processos neuropatológicos, através do mecanismo chamado excitotoxicidade. Por outro lado, o exercício físico induz efeitos positivos no sistema nervoso de mamíferos. Neste trabalho, investigamos, em ratos sedentários e exercitados, os efeitos neurais do MSG, administrado por via orogástrica (gavagem) ou por aplicação tópica cerebral. Ratos Wistar receberam MSG (2 ou 1g/kg, respectivamente; grupos MSG-2 e MSG-1), ou água (grupo controle), nos dias pós-natais (P) 7 a 27. No P28-33, os três grupos foram subdivididos em exercitados (esteira motorizada, 3 semanas, 5 dias/semana, 30 minutos/dia) ou sedentários. No P53-60, sob anestesia, registramos o fenômeno designado como depressão alastrante cortical (DAC). Como observado previamente (tratamento subcutâneo), o tratamento com MSG por gavagem aumentou a velocidade da DAC de maneira dose-dependente comparado com grupo controle. O exercício diminuiu essa aceleração, sugerindo que exerceu influência no desenvolvimento e função cerebral. Três grupos adicionais sem tratamento prévio receberam, durante o registro da DAC, aplicação tópica cortical de MSG em três concentrações (25, 50 e 75 mg/ml). O MSG tópico, ao contrário da gavagem, reduziu a velocidade da DAC de forma reversível, dependente da concentração. Os resultados opostos (MSG por gavagem facilitou, e topicamente dificultou a DAC) sugerem mecanismos de atuação diferentes. Sugere-se cuidado em utilizar MSG como reforçador do sabor dos alimentos, principalmente no organismo em desenvolvimento. / Monosodium glutamate (MSG) is an excitatory amino acid used as a food flavor enhancer ("flavoring agent"). MSG administered to newborn rats in systemic and repetitive way is involved in a wide range of pathological processes, through the mechanism called excitotoxicity. On the other hand, exercise induces a positive effect on the mammalian nervous system. In this work, we investigated the phenomenon known as cortical spreading depression (CSD), in rats treated with MSG and/or treadmill exercise. In addition, we studied the effect of cortical topical treatment with MSG on the CSD parameters. Wistar rats received per gavage MSG (2 or 1g / kg, respectively; MSG-2 and MSG-1 groups) or water (control group) in postnatal days (P) 7 to 27. In P28-33, the three groups were subdivided in exercised (treadmill, 3 weeks, 5 days/week, 30 minutes/day) or sedentary. At P53-60, we recorded the CSD and analyzed its propagation velocity, amplitude and duration. Confirming previous observations, MSG administered per gavage increased the CSD velocity in a dose-dependent manner compared with control group, and the treadmill exercise diminished this acceleration, suggesting that it influenced brain development and functioning. Three additional groups, previously untreated, were used to investigate the effect of topical application of three different concentrations of MSG (25, 50 and 75 mg/ml) during the electrophysiological recording. In contrast to the gavage treatment, topical treatment with MSG reduced significantly and reversibly the CSD propagation velocity. The opposite results suggest different mechanisms for gavage and topical action of MSG. Data suggest caution in the use of MSG as a reinforcer of food flavor, especially in the developing organism.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-08-07T14:37:31Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) DISSERTAÇÃO MESTRADO_LARISSA BRITO-RG.pdf: 842393 bytes, checksum: 7e14b33afc3df50dad2cfe57c1a8a47b (MD5) / Made available in DSpace on 2017-08-07T14:37:31Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) DISSERTAÇÃO MESTRADO_LARISSA BRITO-RG.pdf: 842393 bytes, checksum: 7e14b33afc3df50dad2cfe57c1a8a47b (MD5) Previous issue date: 2016-02-18 / CNPQ / O soro do leite de cabra (SORO), subproduto geralmente descartado durante a fabricação do queijo, é uma boa fonte de ácido siálico (Sia), oligossacarídeo envolvido em processos como memória e excitabilidade cerebral. Neste estudo, investigamos em ratos os efeitos do SORO em pó sobre a memória e a depressão alastrante cortical (DAC), fenômeno relacionado à excitabilidade cerebral, fornecendo evidências para o envolvimento do Sia nesse efeito. Além disso, avaliamos se a deficiência nutricional modularia a ação do SORO. Ratos Wistar foram amamentados em ninhadas com 9 e 15 filhotes (grupos L9 e L15, respectivamente). Nos dias pós-natais (P) 7 a 14, os animais receberam por gavagem 17,45 g/kg/d de SORO, ou Sia (20 mg/kg/d, ou 100 mg/kg/d). No P28-30, testamos a memória dos animais (tarefa de reconhecimento de objetos, TRO). No P35-45 registramos a DAC e analisamos a sua velocidade de propagação, amplitude e duração. Na TRO, os ratos L15 tratados com o SORO obtiveram melhor desempenho do que os controles-L15. Os ratos L15 exibiram velocidades da DAC mais elevadas em comparação com os grupos L9. Os grupos SORO e Sia exibiram velocidade da DAC mais elevada que os grupos naïve e salina, independentemente do estado de lactação (p<0,05). Nossos resultados documentaram este efeito do SORO na memória e DAC. Sia facilitou a DAC de forma dose-dependente, sugerindo seu envolvimento nessa ação do SORO. Este é considerado um suplemento potencial para melhorar a função e desenvolvimento do cérebro em crianças desnutridas. Mais estudos são necessários para investigar tal potencial. / Goat Whey, a usually discarded byproduct from goat cheese manufacturing, is a good source of sialic acid (SA), an oligosaccharide that is involved in processes such as memory and brain excitability. Here, we investigated in rats the effect of dried goat whey (DGW) on memory and the brain excitability-dependent phenomenon known as cortical spreading depression (CSD). We also provide evidence for the involvement of SA in this effect. In addition, we tested animals under unfavorable suckling conditions to evaluate whether nutritional deficiency would modulate DGW action. Wistar rats were suckled in litters with 9 and 15 pups (groups L9 and L15, respectively). From postnatal (P) days 7 to 14, the animals received per gavage 17.45 g of DGW/kg/d, or SA (20 mg/kg/d, or 100 mg/kg/d). At P28-30, we tested the animals‟ memory in the object recognition paradigm. At P35-45 we recorded CSD and analyze its velocity of propagation, amplitude, and duration. In the object recognition test, the L15 DGW-treated rats performed better than the L15-controls. The L15 rats displayed higher CSD velocities compared with L9 groups. The DGW and SA groups exhibited higher CSD velocity than the naïve- and saline-treated controls, regardless the lactation status (p <0.05). Our results documented a novel effect of DGW on memory and CSD. SA dose-dependently facilitated CSD, suggesting its involvement on the DGW action. DGW is considered a potential supplement to improve brain development and function in malnourished children, and this shall be further translationally investigated.