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La malnutrición proteínica prenatal produce mayores alteraciones en la morfología del hipocampo de ratas adultas que en las ratas jóvenes. Sin embargo, no se conoce si hay diferencias por género. En el presente estudio se estimó el volumen del stratum de las células granulares (SCG) y del sistema de fi bras musgosas (SFM) en ratas macho y hembra de 30 días de edad, Sprague-Dawley, que nacieron de madres nutridas con dieta normal (25%) o malnutridas con sólo 6% de caseína durante la gestación. Al nacimiento, las crías se mezclaron y fueron asignadas a madres nodrizas alimentadas con dieta de 25% de caseína y mantenidas con esta dieta hasta su sacrifi cio. Se formaron cuatro grupos de ratas experimentales: 1) machos testigo, 2) machos malnutridos prenatalmente, 3) hembras testigo y 4) hembras malnutridas prenatalmente. Se perfundieron y procesaron con el método de Timm cinco cerebros de cada grupo experimental. En cada uno se estimó el volumen mediante el principio de Cavalieri y se analizaron en el giro dentado: a) el volumen del SCG, los haces b) supra, c) infrapiramidal más la región del hilus y d) volumen total del SFM. No se hallaron efectos signifi cativos por género en las mediciones del SCG en animales testigo. Sin embargo, el volumen total del SFM y el haz suprapiramidal disminuyó signifi cativamente en ratas hembras testigo con respecto la rata macho testigo. Además, en la rata hembra de 30 días, todas las regiones del SCG y el SFM fueron significativamente menores en comparación con las ratas macho malnutridas prenatalmente. Así, este estudio soporta la hipótesis de que el volumen del hipocampo muestra efectos diferenciales debido a las diferencias sexuales, en ratas en especial si se ha sufrido malnutrición prenatal.

A natureza das respostas de medo em animais expostos a situações ameaçadoras depende da intensidade e da distância do estímulo aversivo. Esses estímulos podem ser potencialmente perigosos, distais ou proximais ao animal. Esforços têm sido feitos no sentido de identificar os circuitos neurais recrutados na organização das reações defensivas a estas condições aversivas. Neste artigo, sumarizamos evidências que associam os sistemas cerebrais de defesa ao conceito de medo-stress-ansiedade. Respostas de orientação ao estímulo de perigo, à esquiva e à preparação para o enfrentamento do perigo parecem estar associados à ansiedade. O giro do cíngulo e o córtex pré-frontal de um lado; o núcleo mediano da rafe, septo e o hipocampo de outro fazem parte dos circuitos cerebrais que integram essas respostas emocionais. No outro extremo, estímulos de medo que induzem formas ativas de defesa, mas pouco elaboradas, determinam estados emocionais de natureza diferente e parecem associadas a manifestações elementares de medo. A substância cinzenta periaquedutal dorsal constitui o principal substrato neural para a integração desses estados aversivos no cérebro. Comportamentos defensivos desse tipo são produzidos pela estimulação elétrica e química desta estrutura. À medida que os estímulos ameaçadores, potenciais e distais dão lugar a estímulos de perigo muito intensos ou são substituídos por estímulos proximais de medo, ocorre uma comutação (switch) dos circuitos neurais usualmente responsáveis pela produção de respostas condicionadas de medo para reações defensivas com baixo nível de regulação e organização que se assemelham aos ataques de pânico. Portanto, dependendo da natureza do evento estressor ou do estímulo incondicionado, o padrão de respostas defensivas orientadas e organizadas cede lugar a respostas motoras incoordenadas e incompletas. A amígdala e o hipotálamo medial podem funcionar como uma espécie de interface comutando os estímulos para os substratos neurais apropriados para elaboração das respostas defensivas condicionadas ou incondicionadas. The dangerous stimuli may be potentially dangerous, distal or proximal and the recognition by the animals of each one of these conditions is determinant for the nature of the fear responses. In the present article a parallel with this particular process is drawn taking into account that different fear responses are generated by light, tones and contexts used as conditioned stimuli and by unconditioned stimulation of the dorsal periaqueductal gray (dPAG). In this review we summarize the efforts that have been made to characterize the neural circuits recruited in the organization of defensive reactions to the conditioned and unconditioned aversive stimulations, particularly evidence linking the brain's defense response systems to the concept of fear-stress-anxiety. The dPAG constitute the main neural substrates for the integration of aversive states in response to proximal aversive stimuli. In fact, panic-like behaviors often result when this structure is electrically or chemically stimulated. On the other hand, successful preparatory processes of danger-orientation and preparedness to flee seem to be linked to anxiety. The pre-frontal and cingulate cortex, median raphe nucleus, septum and hippocampus seem to be implicated in the elaboration and organization of these responses. As a working hypothesis, it is advanced that increasing the intensity and proximity of the danger may lead to an emotional shift. When the animals are submitted to this gradual increase in aversiveness there is a switch from the neural circuits responsible for the production of the orientated and organized motor patterns of appropriate defensive response to a conditioned stimulus towards the incomplete and uncoordinated defense responses related to panic attacks. The circuits in the amygdala and the medial hypothalamus responsible for the organization of the defense reaction may well subserve to this switch process.

Las células madre neuronales son células capaces de generar tejido neuronal o que provienen del sistema nervioso, tienen capacidad para la autorenovación y pueden generar otros tipos de células distintas a ellas mismas a través de un proceso de división celular asimétrico. Para las neurociencias las células madre son importantes dada la alta incidencia de trastornos derivados del daño cerebral adquirido, o de consecuencia genética entre la población general. La reparación del daño cerebral es uno de los objetivos centrales de la investigación con células madre, pero ello no es plenamente posible sin una investigación básica en neuropsicología ya que los neuropsicólogos son los que mejor conocen la función cerebral. Existen unas limitadas excepciones de capacidad de neurogénesis en el cerebro que hacen aún más necesaria la neuropsicología en esta área: en los mamíferos adultos existen células madre neuronales que están continuamente generando nuevas neuronas, éstas son la zona subventricular del ventrículo lateral, y las capas subgranulares del giro dentado hipocámpico. Un gran debate social y ético se esta produciendo en la actualidad sobre la legitimidad de la utilización de embriones humanos para la investigación y el desarrollo previsible del uso de células madre embrionarias. En nuestra opinión, el mundo y la sociedad han cambiado lo suficiente para permitir avances que cambiarán la forma de vivir, de enfermar y de sanar. Se necesita un esfuerzo de consenso y una mirada hacia lo positivo con todos los controles que sean necesarios. Neural stem cells are those which are capable of generating neural tissue or that come from the nervous system, have the capacity for self-renewal and can generate different types of cells through a process of symmetric cell division. In neuroscience, stem cells are very important given the high incidence of disorders derived from acquired brain injury, or from genetic consequences. Repairing brain injury is one of the main objectives in stem cell research but it is not fully possible without basic research in neuropsychology since neuropsychologists are those who know the most about brian functions. There are limited exceptions with a capacity for neurogenesis in the brain that makes neuropsychology so important in this area. Adult mammals have neuronal stem cells which are continously generating new neurons in two areas: the subventricular zone of the lateral ventricle and the subgranular layers of the hippocampus dentate gyrus. A tremendous socila and ethical debate is taking place about the legitimacy of using human embryons for research and future development in the use of embryonic stem cells. In our opinion, society and the world have changed sufficiently in order to facilitate the advances which have changed in our lives, illness and cures. What is needed is an effort towards consensus and lloking at the positive side, as well as necessary controls.

Muscarinic Cholinergic receptors of the subtype M4 are G protein coupled receptors that activate Gi reducing AMPc concentration on the cell and closing K+ channels, causing hyperpolarization of the cell membrane and reduction of neurotransmitter release [1]. Previous works from our laboratory using the very selective Muscarinic Toxin 3 (MT3) to block M4 receptors showed that infusion of this substance into the dorsal hippocampus impairs memory consolidation [2] and facilitates memory retrieval [3], suggesting an important role for M4 modulation of CA1 circuitry in memory processes. Also, local application of this toxin in hippocampal slices was able to impair long-term potentiation (LTP) [4]. One hypothesis raised to explain these findings suggests that plastic changes taking place in the CA1 circuitry involves differential control of local excitatory cells and inhibitory interneurons. Since changes in LTP can be elicited by different mechanisms, the objective of this work was to verify, through an analog of the pharmacological infusion used in the behavioral studies, the effect of MT3 on LTP and the activity of inhibitory interneurons as possible targets of this cholinergic action. Thus, we recorded fEPSP from Schaffer collaterals at hippocampal CA1 area of rats anesthetized under urethane. After setting the position and the stimulation intensity to obtain 50% of maximum fEPSP, we recorded 10 min baseline followed by drug infusion (0.5μl, 20μl/h) through a delicate cannula glued to the recording electrode at the contralateral side of stimulae. We infused either MT3 (2.0μg), baclofen (0.1μg), MT3+baclofen (same doses), or their vehicles. After 15min, we applied a high frequency stimulation (HFS) protocol (10 trains at 0.5Hz of 20 pulses 100Hz) and recorded the fEPSP for at least 90min. None of the treatments affected the baseline excitability. Our results indicate that: MT3 infusion 15min before HFS was able to block LTP, consistent with our previous finding with MT3 applied 2min before HFS [4], and baclofen, a GABAB receptor agonist in a subeffective dose, was able to prevent this MT3 effect. Considering that hippocampal GABAB receptors are mainly presynaptic and mostly located in GABAergic interneurons, and that its activation leads to cell hyperpolarization / reduction of GABA release, our results suggest that the M4 receptors relevant to those behavioral responses may be colocalized with GABAB receptors in the CA1 interneurons. Further studies are necessary to verify this hypothesis.

OBJETIVOS: Obtenção de dados do espectro de metabolitos por ressonância magnética da formação hipocampal no idoso normal e com doença de Alzheimer (DA). MÉTODO: Os indivíduos foram pareados por idade, sendo 20 na amostra normal, CDR=0 e 40 com DA 3 CDR=1 e 2. Utilizou-se aparelho Signa Horizon LX-GE, 1.5T, ¹H-ERM com aplicativo automatizado PROBE/SV, VOI: hc (direito e esquerdo); voxel único (2x2x2cm); TR 1500ms/TE 50ms; PRESS; metabolitos: N-acetilaspartato (Naa), colina (Cho), creatina (Cr), mio-inositol (mI). RESULTADOS: Os presentes dados se referem aos quocientes de Naa, Cho e mI, com Cr tomada como referência e relação mI/Naa. O estudo mostrou o Naa reduzido, o mI e a relação mI/Naa aumentados e os resultados em relação à Cho foram variados. Os resultados da amostra global dos pacientes com DA em comparação à média ± dp da amostra normal foram significativos para Naa, mI e mI/Naa (p

Before 1960, the brain was considered by scientists to be immutable, subject only to genetic control. In the early sixties, however, investigators were seriously speculating that environmental influences might be capable of altering brain structure. By 1964, two research laboratories proved that the morphology and chemistry or physiology of the brain could be experientially altered (Bennett et al. 1964, Hubel and Wiesel 1965). Since then, the capacity of the brain to respond to environmental input, specifically "enrichment,'' has become an accepted fact among neuroscientists, educators and others. In fact, the demonstration that environmental enrichment can modify structural components of the rat brain at any age altered prevailing presumptions about the brain's plasticity (Diamond et al. 1964, Diamond 1988). The cerebral cortex, the area associated with higher cognitive processing, is more receptive than other parts of the brain to environmental enrichment. The message is clear: Although the brain possesses a relatively constant macrostructural organization, the ever-changing cerebral cortex, with its complex microarchitecture of unknown potential, is powerfully shaped by experiences before birth, during youth and, in fact, throughout life. It is essential to note that enrichment effects on the brain have consequences on behavior. Parents, educators, policy makers, and individuals can all benefit from such knowledge.Antes de 1960, os cientistas consideravam o encéfalo como imutável, sujeito apenas ao controle genético. Entretanto, no início dos anos 60, alguns pesquisadores especulavam seriamente que influências ambientais podiam ser capazes de alterar a estrutura cerebral. Por volta de 1964, dois laboratórios de pesquisa demonstraram que a morfologia e a química ou a fisiologia do cérebro poderia ser modificada pela experiência (Bennett et al. 1964, Hubel e Wiesel 1965). Desde então, a capacidade do cérebro a responder para responder a insumos ambientais, especificamente ao "enriquecimento'', tornou-se um fato aceito por neurocientistas, educadores e outros. De fato, a demonstração de que o enriquecimento ambiente pode modificar componentes estruturais do cérebro de rato, em qualquer idade, alterou suposições prevalentes a respeito da plasticidade cerebral (Diamond et al. 1964, Diamond 1988). O córtex cerebral, a área associada com o processamento cognitivo superior, é mais receptivo do que outras partes do encéfalo ao enriquecimento ambiental. A mensagem é clara: embora o encéfalo possua uma organização macro-estrutural relativamente constante, o sempre-mutável córtex cerebral, com sua microarquitetura complexa de potencial desconhecido, é fortemente moldado pelas experiências antes do nascimento, durante a juventude e, em verdade, ao longo de toda a vida. É essencial que se note que os efeitos do enriquecimento sobre o encéfalo têm consequências no comportamento. Pais, educadores, geradores de políticas e quaisquer indivíduos podem todos se beneficiar de tal conhecimento.

The present work shows effects of pentoxifylline (ptx) on learning and memory in rats with hippocampal lesion induced by glutamate (glu). The animais (male Wistar rats, 200- 250g) were submitted to stereotaxic surgery and injected in the hippocampus (CAI, CA3) with glu at doses of 24, 48, 96 and 192 pg. After 7 days, animais were tested in the open-field to evaluate locomotor activity and submitted to memory tests (passive avoidance, elevated T maze, and water maze). Twenty-four hours later, animais were sacrificed for histopathological studies. The results show no significant lesion in the saline and glu (24 and 48 pg) groups. However, moderate to severe lesions were observed at higher glu doses (96 and 192 pg). Increased locomotor activity after glu as compared to Controls was observed only with the dose of 192 pg (saline: 14,82 ± 2,59, glul92: 31,10 ± 6,50 squares). In the passive avoidance test the groups treated with glu 48, 96 and 192 pg, showed memory deficits, in early memory (saline: 200,43 ± 52,09; glu24: 210,20 ± 44,77; glu48: 27,61 ± 9,89; glu96: 64,46 ± 31,93; glu 192: 140,29 ± 40,76s), as well as in the late memory (saline: 252,57 ± 31,78; glu24: 273,70 ± 22,27; glu48: 44,35 ± 32,21; glu96: 29,39 ± 14,54, glul92: 140,29 ± 40,76s). In the elevated T-maze, animais treated with glu at higher doses showed a lower performance as compared to Controls. Analyses of memory retention in the water maze showed defict in spatial memory (saline: 10,95 ± 3,56, glu96: 26,89 ± 3,97, glu 192: 32,79 ± 4,78s). Ptx at lOOmg/kg, protected animais against glu(96 pg)-induced lesion. Besides ptx did not alter locomotion activity, but when injected in lesioned animais an increased locomotor activity was observed. In the elevated T-maze, ptx-treated animais presented a better performance, decreased the deficits produced by glu (Avoidance 3- saline: 188,51 ± 26,66, glu96: 144,76 ± 33,74, ptxlOO: 293,55 ± 6,44, ptx200: 185,25 ± 32,45, ptxlOO+glu: 237,42 ± 29,06, ptx200+glu: 168,32 ± 41,07s) (KW, p

A total of 182 young adult male Wistar rats were bilaterally implanted with cannulae into the CA1 region of the dorsal hippocampus and into the amygdaloid nucleus, the entorhinal cortex, and the posterior parietal cortex. After recovery, the animals were trained in a stepdown inhibitory avoidance task. At various times after training (0, 30, 60 or 90 min) the animals received a 0.5-μl microinfusion of vehicle (saline) or 0.5 μg of muscimol dissolved in the vehicle. A retention test was carried out 24 h after training. Retention test performance was hindered by muscimol administered into both the hippocampus and amygdala at 0 but not at 30 min posttraining. The drug was amnestic when given into the entorhinal cortex 30, 60 or 90 min after training, or into the parietal cortex 60 or 90 min after training, but not before. These findings suggest a sequential entry in operation, during the posttraining period, of the hippocampus and amygdala, the entorhinal cortex, and the posterior parietal cortex in memory processing.

Journal Article; Research Support, Non-U.S. Gov't; Soy extracts have been claimed to be neuroprotective against brain insults, an effect related to the estrogenic properties of isoflavones. However, the effects of individual isoflavones on obesity-induced disruption of adult neurogenesis have not yet been analyzed. In the present study we explore the effects of pharmacological administration of daidzein, a main soy isoflavone, in cell proliferation, cell apoptosis and gliosis in the adult hippocampus of animals exposed to a very high-fat diet. Rats made obese after 12-week exposure to a standard or high-fat (HFD, 60%) diets were treated with daidzein (50 mg kg(-1)) for 13 days. Then, plasma levels of metabolites and metabolic hormones, cell proliferation in the subgranular zone of the dentate gyrus (SGZ), and immunohistochemical markers of hippocampal cell apoptosis (caspase-3), gliosis (GFAP and Iba-1), food reward factor FosB and estrogen receptor alpha (ERα) were analyzed. Treatment with daidzein reduced food/caloric intake and body weight gain in obese rats. This was associated with glucose tolerance, low levels of HDL-cholesterol, insulin, adiponectin and testosterone, and high levels of leptin and 17β-estradiol. Daidzein increased the number of phospho-histone H3 and 5-bromo-2-deoxyuridine (BrdU)-ir cells detected in the SGZ of standard diet and HFD-fed rats. Daidzein reversed the HFD-associated enhanced immunohistochemical expression of caspase-3, FosB, GFAP, Iba-1 and ERα in the hippocampus, being more prominent in the dentate gyrus. These results suggest that pharmacological treatment with isoflavones regulates metabolic alterations associated with enhancement of cell proliferation and reduction of apoptosis and gliosis in response to high-fat diet. Yes

Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laboratory of Investigations in Neurodegeneration and Infection. Bel?m, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laboratory of Investigations in Neurodegeneration and Infection. Bel?m, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laboratory of Investigations in Neurodegeneration and Infection. Bel?m, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laboratory of Investigations in Neurodegeneration and Infection. Bel?m, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Neuroanatomia Funcional. Bel?m, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Neuroanatomia Funcional. Bel?m, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Neuroanatomia Funcional. Bel?m, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Neuroanatomia Funcional. Bel?m, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Neuroanatomia Funcional. Bel?m, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Neuroanatomia Funcional. Bel?m, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laboratory of Investigations in Neurodegeneration and Infection. Bel?m, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laboratory of Investigations in Neurodegeneration and Infection. Bel?m, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laboratory of Investigations in Neurodegeneration and Infection. Bel?m, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laboratory of Investigations in Neurodegeneration and Infection. Bel?m, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laboratory of Investigations in Neurodegeneration and Infection. Bel?m, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Neuroanatomia Funcional. Bel?m, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laboratory of Investigations in Neurodegeneration and Infection. Bel?m, PA, Brasil.

The first steps of the discovery, and the main discoverers, of the hippocampus are outlined. Arantius was the first to describe a structure he named "hippocampus" or "white silkworm". Despite numerous controversies and alternate designations, the term hippocampus has prevailed until this day as the most widely used term. Duvernoy provided an illustration of the hippocampus and surrounding structures, considered the first by most authors, which appeared more than one and a half century after Arantius' description. Some authors have identified other drawings and texts which they claim predate Duvernoy's depiction, in studies by Vesalius, Varolio, Willis, and Eustachio, albeit unconvincingly. Considering the definition of the hippocampal formation as comprising the hippocampus proper, dentate gyrus and subiculum, Arantius and Duvernoy apparently described the gross anatomy of this complex. The pioneering studies of Arantius and Duvernoy revealed a relatively small hidden formation that would become one of the most valued brain structures.Os primeiros passos no descobrimento e os principais descobridores do hipocampo são aqui rastreados. Arantius foi o primeiro a descrever uma estrutura que designou "hipocampo" ou "bicho-da-seda branco". Apesar de muitas controvérsias e denominações alternativas, o termo hipocampo prevaleceu até os dias atuais como o mais amplamente utilizado. Duvernoy apresentou uma ilustração do hipocampo e estruturas próximas, considerada a primeira, de acordo a maioria dos autores, que apareceu mais de um e meio século depois da descrição de Arantius. Alguns autores identificaram outras figuras e textos, que supostamente antedataram os de Duvernoy, nas obras de Vesalius, Varolio, Willis e Eustachio, mas não de modo inequívoco. Considerando a definição da formação hipocampal como compreendendo a hipocampo propriamente dito, giro denteado e subículo, Arantius e Duvernoy aparentemente descreveram a anatomia macroscópica deste complexo. Os estudos pioneiros de Arantius e Duvernoy revelaram uma formação relativamente pequena e ocultada que se tornaria uma das estruturas cerebrais mais valorizadas.

This paper compiles several studies that show the relationship between bilingualism and Alzheimer’s disease. Studies here compiled were independently carried out between 1991 and 2012 in the United States, in Canada, in the United Kingdom, in India and in Sweden. the paper reviews the results of studies that show that the time elapsed between early Alzheimer’s diagnosis and the actual appearance of telltale symptom is up to five years longer in elderly bilinguals than in elderly monolinguals. Cradle bilinguals benefit most from bilingualism but language learning in adulthood can also benefits speakers. These and related scientific facts are compiled. Reports of scientific research are presented, and its conclusions are summarized. Resumen Este paper recompila estudios que muestran la relación existente entre el bilingüismo y el mal de Alzheimer. Los estudios se realizaron independientemente entre 1991 y 2012 en Estados Unidos, en el Canadá, en el Reino Unido, en la India y en Suecia. El paper revisa los resultados de estos estudios que muestran que el tiempo que transcurre entre el diagnóstico precoz de Alzheimer’s y la presentación de los primeros síntomas es hasta cinco años más demorado en ancianos bilingües que en ancianos monolingües. Quienes más se benefician del bilingüismo son los que han sido bilingües desde la cuna, pero también se ha demostrado que se benefician los hablantes que aprenden idiomas en la adultez. Tanto estos como otros hechos científicos relacionados se presentan y se resumen sus conclusiones.

Em termos biológicos, o stresse representa qualquer estímulo percepcionado pelo organismo como uma ameaça (potencial ou real) para o seu equilíbrio. Quando confrontados com estímulos stressantes, os organismos vivos iniciam uma série de respostas com vista à manutenção da homeostasia e à formação de memórias que permitam respostas proporcionadas em situações idênticas futuras. Contudo, quando activados contínua ou excessivamente, os sistemas de resposta ao stresse podem tornar-se prejudiciais, condicionando défices funcionais importantes, info:eu-repo/semantics/publishedVersion

Tese de mestrado integrado, Engenharia Biomédica e Biofísica, Universidade de Lisboa, Faculdade de Ciências, 2019 Submitted by Teresa Boa (tdboa@fc.ul.pt) on 2020-02-03T11:39:08Z No. of bitstreams: 1 ulfc125747_tm_Raquel_Ferreira.pdf: 3756369 bytes, checksum: d9a0e6aeae0ab5cfeae568bf0c4ed4f7 (MD5) Made available in DSpace on 2020-02-03T11:39:24Z (GMT). No. of bitstreams: 1 ulfc125747_tm_Raquel_Ferreira.pdf: 3756369 bytes, checksum: d9a0e6aeae0ab5cfeae568bf0c4ed4f7 (MD5) Previous issue date: 2019

Aquesta pretén ser una revisió general dels processos cognitius normals i de la capacitat de reorganització cerebral en cas de dany cerebral adquirit (lesions i malalties neurodegeneratives). Esta pretende ser una revisión general de los procesos cognitivos normales y de la capacidad de reorganización cerebral en caso de daño cerebral adquirido (lesiones y enfermedades neurodegenerativas). Bachelor thesis for the Psychology program.

OBJECTIVE: The hippocampus has an important role in the acquisition and recall of aversive memories. The objective of this study was to investigate the relationship among hippocampal rhythms. METHODS: Microeletrodes arrays were implanted in the hippocampus of Wistar rats. The animals were trained and tested in a contextual fear conditioning task. The training consisted in applying shocks in the legs. The memory test was performed 1 day (recent memory) or 18 days (remote memory) after training. We proposed a measure based on the FFT power spectrum, denominated "delta-theta ratio", to characterize the different behaviors (active exploration and freezing) and the memories types. RESULTS: The delta-theta ratio was able to distinguish recent and remote memories. In this study, the ratio for the 18-day group was smaller than for the 1-day group. Moreover, this measure was useful to distinguish the different behavior states – active exploration and freezing. CONCLUSIONS: The results suggest delta-theta oscillations could reflect the demands on information processing during recent and remote memory recalls. OBJETIVO: O hipocampo tem um importante papel na aquisição e evocação das memórias aversivas. Pretendeu-se, neste trabalho, investigar a dinâmica entre os ritmos hipocampais durante a evocação das memórias aversivas recente e remota. MÉTODOS: Foram implantadas matrizes de microeletrodos em ratos Wistar. Os animais foram treinados e testados numa tarefa de condicionamento contextual de medo. O treino consistiu em aplicações de choques nas patas. O teste de memória foi realizado 1 dia (memória recente) ou 18 dias (memória remota) após o treino. Nesse trabalho, foi proposta uma medida baseada no espectro de potências, denominada "razão delta-theta", para caracterização dos diferentes comportamentos observados (vigília exploratória e congelamento) e tipos de memórias. RESULTADOS: A razão delta-theta mostrou-se capaz de distinguir os grupos testados para as memórias recente e remota. Neste caso, observou-se, para o grupo testado 18 dias após, um valor menor do que para o grupo testado 1 dia após. Além disso, essa medida mostrou-se útil para distinguir os diferentes estados comportamentais. CONCLUSÕES: Os resultados sugerem que a dinâmica entre os ritmos delta e theta pode refletir o processamento da informação durante a evocação das memórias recente e remota.

Teses de Mestrado em Bioquímica, apresentada ao Departamento de Ciências da Vida da Faculdade de Ciências e Tecnologia da universidade de Coimbra. Demonstrámos recentemente, que uma dose única e elevada de metanfetamina (METH) causou um fenótipo depressivo de longa duração, aferido pelo aumento do tempo de imobilidade no teste de tail suspension. Tem sido demonstrado que o exercício físico alivia os sintomas depressivos. Propomo-nos confirmar e caracterizar mais detalhadamente o fenótipo depressivo causado por uma única injecção neurotóxica de METH e investigar a correlação entre a homeostase de 5-HT no córtex frontal e hipocampo e o efeito antidepressivo de exercício físico. Murganhos adultos C57BL/6 foram submetidos a um programa de exercício em treadmill (cinco dias por semana durante sete semanas) a partir de 24 h após uma única dose elevada de METH (30 mg/kg, i.p.), tendo sido organizados da seguinte forma (n=8/grupo): salino/sedentário; METH/sedentário; salino/exercício e METH/exercício. Em seguida, avaliou-se a exploração/actividade locomotora, anedonia e desespero (comportamentos do tipo depressivo) numa fase tardia da privação de METH (49 dias) através dos testes open-field, splash e forced-swim, respectivamente. Os teores totais de 5- HT no cortex-frontal e hipocampo (49 dias pós-METH) foram avaliados por cromatografia líquida de fase reversa e de alta eficiência (HPLC). Avaliámos o impacto inicial (3 dias pós-METH) de METH nos níveis totais de 5-HT do hipocampo noutro grupo de murganhos (16). É importante registar que a METH diminuiu o tempo de grooming dos murganhos sedentários, no teste splash. Isto demonstra que esta dose de METH induz um comportamento do tipo anedónico. Por outro lado, confirmou-se ainda que a METH induz um comportamento do tipo depressivo de longa duração. Além disso, o exercício em treadmill reverteu o tempo de grooming no teste splash, 7 semanas após a injecção de METH. Este efeito antidepressivo foi ainda aferido por uma diminuição do tempo de imobilidade e um aumento do tempo de natação no teste forced-swim exibido pelos murganhos, control ou submetidos à METH. Adicionalmente, o exercício aumentou a actividade locomotora, o comportamento exploratório e a razão distância central - distância total nos murganhos control ou submetidos à METH no teste open-field. Isto é consistente com o facto de o exercício físico induzir um estado de bem-estar emocional, independentemente do tratamento farmacológico. Por outro lado, a METH não alterou significativamente os parâmetros motores de murganhos sedentários. Isto é relevante, vistoque sugere que a actividade locomotora não contribuiu para o comportamento do tipo anedónico observado. A análise neuroquímica mostrou que a METH provocou uma deplecção robusta de 5-HT no hipocampo nos primeiros 3 dias após a injecção de METH, que foi recuperada 49 dias após o tratamento. Além disso, o exercício físico não teve um impacto significativo nos níves hipocampais de 5-HT. Adicionalmente, nem o exercício físico nem a METH alteraram significativamente os teores toatis de 5-HT. É importante destacar, que demostrámos que um programa de sete semanas de exercício em treadmill promoveu um efeito antidepressivo em murganhos intoxicados com METH. No entanto, este benefício do exercício não está associado a altenações na homeostase serotonérgica fronto-cortical/hipocampal. Recently we demonstrated that a single high neurotoxic dose of methamphetamine (METH) caused a long-lasting depressive phenotype as gauged by increased immobility time in the tail suspension test. It has been shown that physical exercise alleviates depressive symptoms. This study aims to further characterize the long-term depressive phenotype caused by a single neurotoxic METH-injection and to probe for a correlation between frontalcortical and hippocampal 5-HT homeostasis and the antidepressant effect of physical exercise. Adult C57BL/6 mice were submitted to a treadmill exercise program (five days a week for seven weeks) starting 24 h post-single high dose of METH (30 mg/kg, i.p.) and were organized as follows (n=8/group): saline/sedentary; METH/sedentary; saline/exercise and METH/exercise. Then, we assessed the exploration/locomotor activity, anhedonia and despair (depressive-like behaviours) at a late stage of METH withdrawal (49 days) by open-field, splash and forced-swim tests, respectively. Frontal cortical and hippocampal (49 days post-METH) levels of 5-HT were evaluated by reversed-phase high performance liquid chromatography (HPLC). Another set of mice (16) was used to evaluate early impact (3 days post-METH) of METH on 5-HT hippocampal levels. Remarkably METH decreased the time that sedentary mice spent grooming. This shows that this METH dose induces anhedonia-like behavior. This further confirms that METH induces a long-lasting depressive-like behaviour. Remakably treadmill exercise reversed the time mice spent grooming in the splash test 7 weeks post-injection. This antidepressant-like effect was further gauged by a decreased immobility time and increased swimming time in the forced swimming test exhibited by both saline- and METHexercised animals. Additionally, exercise increased locomotor activity, exploratory behavior and the central distance – total distance ratio in both saline and METH treated mice in the open field. This is consistent with physical exercise inducing a high-mood state, irrespectively of drug treatment. On the other hand, METH did not alter significantly the motor parameters from sedentary mice. This is relevant since locomotor activity did not contribute to the anhedonic-like behavior seen herein. The neurochemical analysis showed that METH triggered a robust 5-HT hippocampal depletion as early as 3 days post-METH, which recovered 49 days post-tretament. Additionally, physical exercise failed to have anysignificant impact on hippocampal 5-HT levels. Moreover, neither METH nor physical exercise altered frontal cortical 5-HT levels. Importantly, we present new evidence that a 7 weeks treadmill program provided an antidepressant effect to METH-intoxicated mice. This exercise benefit is not associated with changes in the frontal cortical/hippocampal serotonergic homeostasis.

Background The GABAergic system plays an important role in modulating levels of anxiety. When transplanted into the brain, precursor cells from the medial ganglionic eminence (MGE) have the ability to differentiate into GABAergic interneurons and modify the inhibitory tone in the host brain. Currently, two methods have been reported for obtaining MGE precursor cells for transplantation: fresh and neurosphere dissociated cells. Here, we investigated the effects generated by transplantation of the two types of cell preparations on anxiety behavior in rats. Results We transplanted freshly dissociated or neurosphere dissociated cells into the neonate brain of male rats on postnatal (PN) day 2–3. At early adulthood (PN 62–63), transplanted animals were tested in the Elevated Plus Maze (EPM). To verify the differentiation and migration pattern of the transplanted cells in vitro and in vivo, we performed immunohistochemistry for GFP and several interneuron-specific markers: neuropeptide Y (NPY), parvalbumin (PV) and calretinin (CR). Cells from both types of preparations expressed these interneuronal markers. However, an anxiolytic effect on behavior in the EPM was observed in animals that received the MGE-derived freshly dissociated cells but not in those that received the neurosphere dissociated cells. Conclusion Our results suggest a long-lasting anxiolytic effect of transplanted freshly dissociated cells that reinforces the inhibitory function of the GABAergic neuronal circuitry in the hippocampus related to anxiety-like behavior in rats. Electronic supplementary material The online version of this article (doi:10.1186/1471-2202-15-94) contains supplementary material, which is available to authorized users.