Memórias da Infância e da Educação: abordagens eliasianas sobre as mulheres

Relações sociais entre indivíduos estão pautadas pela experiência de educação e formação que cada um traz consigo ao longo da vida, pelo modo como se constituem individual e coletivamente. A partir de Elias e da metodologia da história oral, o objetivo foi buscar nas memórias de infância de sete mulheres, professoras de crianças, nascidas entre 1950 e 1970, a formação e a educação que se constituiu na infância em espaços privados e domésticos. Apreendeu-se que a escolha profissional tem vínculos com a educação feminina, normatizada por regras de controle e civilidade

Structural analysis of adult neural stem cells and their niche in the adult hippocampus

New neurons are constantly produced at the sub-granular zone of the dentate gyrus, this phenomenon is called adult neurogenesis. This process is tightly regulated by several extrinsic factors such as physical activity, enriched environment, hippocampal-dependent learning tasks and a large number of molecules, as well as by intrinsic factors such as the neurogenic niche and the neuronal activity. The adult neural stem cell has a very specific morphology: The cell body is located in the sub- granular zone extend a long radial process that seeps into the granular layer and branches in the first third of the molecular layer. The complex morphology of the neural stem cell, suggests that close contacts with numerous cell types of the neurogenic niche may finely regulate of its proliferation and differentiation. The structure and interactions of the adult neural stem cell with the neurogenic niche are, however, very poorly described. Thus, the work of my thesis was to: - Study the complex morphology of the neural stem cell - Clarify the link between morphology and activity - Study the nature of contact between the components of the neurogenic niche and the RGL neural stem cell - Assess the role of certain cells of the niche in the regulation of proliferation and differentiation of adult neural stem cell. In the adult dentate gyrus, we discovered the existence of two subpopulations of cells with similar morphologies and related to the stem cell: the type α and type β. The type α represents 76 % of all RGL cells, has a long primary process with a small branch on the molecular layer of the dentate gyrus. The type β cell represents 24 % of the cells, has a short primary process with significant branching within the granular layer. The two subpopulations express stem cell markers, while the β cells also co-express astrocytic markers. Using clonal analysis, we showed that the type α divides and gives rise to all cell types (neurons, astrocytes and β cell), while the type β do not divide but is essentially transformed into astrocyte. Thus, a type α morphology contributes to the stem cell ability to capture stimuli within the molecular layer that regulate its proliferation and differentiation. Then, we evaluated the role of glia in the regulation of stem cell in different physiological states: voluntary running and brain aging. We have established that there is an inverse correlation between the activation state of microglia and adult neurogenesis. Similarly, we analyzed the involvement of astrocytes in the regulation of the RGL neural stem cells by testing the effect of two molecules produced by astrocytes. We found that D-serine and taurine stimulate stem cells proliferation and the formation and maturation of new neurons. Our results emphasize the importance of the neurogenic niche in the regulation of the stem cell. This knowledge is crucial for the understanding of homeostasis and brain plasticity, and for the development of brain repair strategies. -- De nouveaux neurones sont constamment produits au niveau de la couche sous-granulaire du gyrus denté, ce phénomène est appelé la neurogenèse adulte. Ce processus est finement régulé par plusieurs facteurs extrinsèques tels que l'activité physique, l'environnement enrichi, les tâches d'apprentissage hippocampiques-dépendantes et un grand nombre de molécules, ainsi que par les facteurs intrinsèques tels que la niche neurogènique et l’activité neuronale. La cellule souche neurale adulte dispose d’une morphologie très particulière pour une cellule souche : Son corps cellulaire est situé dans la couche sous-granulaire et elle projette un long processus radial qui s’infiltre dans la couche granulaire et se ramifie dès le début de la couche moléculaire. La morphologie complexe de la cellule souche neurale, suggère qu’elle établit des contacts étroits avec différents types cellulaires de la niche neurogénique, qui contribuent à sa régulation. La structure et les interactions de la cellule souche neurale adulte avec la niche neurogénique sont cependant très peu décrites. Ainsi, le travail de ma thèse consiste à : - Etudier la morphologie complexe de la cellule souche neurale - Clarifier le lien entre morphologie et activité - Etudier la nature des contacts entre les composants de la niche neurogénique et la cellule souche - Evaluer le rôle de certaines cellules de la niche dans la régulation de la prolifération et de la différenciation de la cellule souche neuronale adulte. Dans le gyrus denté adulte, nous avons decouvert l’existence de deux sous-populations de cellules de morphologies similaires et apparentées à la cellule souche: la type α et la type β. La type α représente 76% de toutes les cellules à morphologie radiaire et possède un processus primaire long avec une ramification modeste au niveau de la couche moléculaire du gyrus denté. La type β représente 24% des cellules à morphologie radiaire et possède un processus primaire court avec une importante ramification à l’intérieur de la couche granulaire. Les deux sous-populations expriment les marqueurs de cellules souches, alors que la cellule β co-exprime également des marqueurs astrocytaires. A l’aide d’une analyse clonale, nous avons montré que la type α se divise et donne naissance à tous types de cellules (neurones, astrocytes et cellule β), alors que la type β ne se divise pas mais se transforme essentiellement en astrocyte. Ainsi, une morphologie de type α accorde à la cellule souche la possibilité de capter des stimuli régulant sa prolifération et sa différenciation au sein de la couche moléculaire. Ensuite, nous avons évalué le rôle de la glie dans la régulation de la cellule souche dans différents états physiologiques : la course volontaire et le vieillissement cérébral. Nous avons établi qu’il existait une corrélation inverse entre l’état d’activation de la microglie et la neurogenèse adulte. De même, nous avons analysé l’implication des astrocytes dans la régulation de la cellule souche en testant l’effet de deux molécules produites par les astrocytes. Nous avons trouvé que la D-serine et la taurine stimulent la prolifération des cellules souches ainsi que la formation et la maturation des nouveaux neurones. Nos résultats soulignent l’importance de la niche neurogénique dans la régulation de la cellule souche. Ces connaissances sont d'une importance cruciale pour la compréhension de l’homéostasie et de la plasticité du cerveau, ainsi que pour la mise en place des stratégies de réparation cérébrale

Taurine increases hippocampal neurogenesis in aging mice

Aging is associated with increased inflammation and reduced hippocampal neurogenesis, which may in turn contribute to cognitive impairment. Taurine is a free amino acid found in numerous diets, with anti-inflammatory properties. Although abundant in the young brain, the decrease in taurine concentration with age may underlie reduced neurogenesis. Here, we assessed the effect of taurine on hippocampal neurogenesis in middle-aged mice. We found that taurine increased cell proliferation in the dentate gyrus through the activation of quiescent stem cells, resulting in increased number of stem cells and intermediate neural progenitors. Taurine had a direct effect on stem/progenitor cells proliferation, as observed in vitro, and also reduced activated microglia. Furthermore, taurine increased the survival of newborn neurons, resulting in a net increase in adult neurogenesis. Together, these results show that taurine increases several steps of adult neurogenesis and support a beneficial role of taurine on hippocampal neurogenesis in the context of brain aging

Mitofusin-2 in nucleus accumbens regulates anxiety and depression-like behaviors through mitochondrial and neuronal actions

Background Emerging evidence points at a central role of mitochondria in psychiatric disorders. However, little is known about the molecular players that regulate mitochondria in neural circuits regulating anxiety and depression, and how they impact on neuronal structure and function. Here, we investigate the role of molecules involved in mitochondrial dynamics in medium spiny neurons (MSNs) from the nucleus accumbens (NAc), a hub of the brain’s motivation system. Methods We assess how individual differences in anxiety (elevated plus maze and open field tests) and depression-like (forced swim and saccharin preference tests) behaviors in outbred rats relate to mitochondrial morphology (electron microscopy and 3D reconstructions) and function (mitochondrial respirometry). Mitochondrial molecules are measured for protein (Western blot) and mRNA (qRT-PCR, RNAscope) content. Dendritic arborization (Golgi sholl analyses), spine morphology, and MSNs excitatory inputs (path-clamp electrophysiology) are characterized. Mitofusin 2 (Mfn2) overexpression in the NAc is induced through an AAV9-syn1-MFN2. Results High anxious animals show increased depression-like behaviors, as well as reduced expression of the mitochondrial GTPase Mfn2 in the NAc. They also show alterations in mitochondria (i.e., respiration, volume, interactions with the endoplasmic reticulum) and MSNs (i.e., dendritic complexity, spine density and typology, excitatory inputs). Viral Mfn2 overexpression in the NAc reverses all these behavioral, mitochondrial and neuronal phenotypes. Conclusions Our results implicate a causal role for accumbal Mfn2 on the regulation of anxiety and depression-like behaviors through actions on mitochondrial and MSN structure and function. Mfn2 is posited as a promising therapeutic target to treat anxiety and associated behavioral disturbances

Synaptic Adhesion Molecules Regulate the Integration of New Granule Neurons in the Postnatal Mouse Hippocampus and their Impact on Spatial Memory

Postnatal hippocampal neurogenesis induces network remodeling and may participate to mechanisms of learning. In turn, the maturation and survival of newborn neurons is regulated by their activity. Here, we tested the effect of a cell-autonomous overexpression of synaptic adhesion molecules on the maturation and survival of neurons born postnatally and on hippocampal-dependent memory performances. Families of adhesion molecules are known to induce pre- and post-synaptic assembly. Using viral targeting, we overexpressed three different synaptic adhesion molecules, SynCAM1, Neuroligin-1B and Neuroligin-2A in newborn neurons in the dentate gyrus of 7- to 9-week-old mice. We found that SynCAM1 increased the morphological maturation of dendritic spines and mossy fiber terminals while Neuroligin-1B increased spine density. In contrast, Neuroligin-2A increased both spine density and size as well as GABAergic innervation and resulted in a drastic increase of neuronal survival. Surprisingly, despite increased neurogenesis, mice overexpressing Neuroligin-2A in new neurons showed decreased memory performances in a Morris water maze task. These results indicate that the cell-autonomous overexpression of synaptic adhesion molecules can enhance different aspects of synapse formation on new neurons and increase their survival. Furthermore, they suggest that the mechanisms by which new neurons integrate in the postnatal hippocampus conditions their functional implication in learning and memory

Amygdala GluN2B-NMDAR dysfunction is critical in abnormal aggression of neurodevelopmental origin induced by St8sia2 deficiency

Aggression is frequently observed in neurodevelopmental psychiatric disorders such as schizophrenia, autism, and bipolar disorder. Due to a lack of understanding of its underlying mechanisms, effective treatments for abnormal aggression are still missing. Recently, genetic variations in Sialyltransferase 2 (St8sia2) have been linked to these disorders and aggression. Here we identify abnormal aggressive behaviors and concomitant blunted fear learning in St8sia2 knockout (−/−) mice. It is worth noting that the amygdala of St8sia2−/− mice shows diminished threat-induced activation, as well as alterations in synaptic structure and function, including impaired GluN2B-containing NMDA receptor-mediated synaptic transmission and plasticity. Pharmacological rescue of NMDA receptor activity in the amygdala of St8sia2−/− mice with the partial agonist d-cycloserine restores synaptic plasticity and normalizes behavioral aberrations. Pathological aggression and associated traits were recapitulated by specific amygdala neonatal St8sia2 silencing. Our results establish a developmental link between St8sia2 deficiency and a pathological aggression syndrome, specify synaptic targets for therapeutic developments, and highlight d-cycloserine as a plausible treatment