Detta examensarbete handlar om hjärnans utveckling, inlärningen och våra inre inlärningsstilar. Det tar också upp kort om hur man kan utnyttja inlärningsstilar i skolan. Syftet har varit att ta reda på hur vi utvecklas och hur de utvecklingsstrukturer ser ut som vi föds med och utvecklar efterhand. De frågeställningar jag haft under skrivandets gång har varit: Vilka är "de sju olika intelligenserna"? Hur utvecklas hjärnan? Var och när börjar vi lära, och vad är det som ligger till grund för vår inlärning? Hur kan man bearbeta olika inlärningsstilar i skolans högre stadier? Den metod jag använt är en litteraturstudie med litteratur som behandlar inlärningen, hjärnans utveckling, hur vi tänker och lär mm. Jag har också besökt en högstadieskola som bedriver viss av sin undervisning med hjälp av olika inlärningsstilar. I projektbeskrivningen beskrivs kortfattat hur man kan använda inlärningsstilar i skolan. I diskussionen har jag behandlat min frågeställning lite mer ingående om saker och ting jag anser mer eller mindre trovärdiga från litteraturen, jag har också dragit en mer eller mindre trovärdig parallell mellan vår utveckling och handlande till hur dagens samhälle ser ut. Jag hoppas att du som läsare känner igen dig i vissa delar eller har lärt dig något av att läsa detta examensarbete, det har i alla fall jag gjort

<p>Several studies have shown that children who grow up under adverse care giving conditions are prone to develop a broad spectrum of different problems, ranging from mild depression to severe psychosomatic pathology later in life. A carefully treated child develops a different attachment strategy and biochemical response than a maltreated child. Early adverse events seem to program the stress response to become either over or under reactive which in turn have the potential to alter brain development. Major consequences include reduced plasticity and abnormal frontal lobe activity. This review further investigates the emotional and cognitive development in children exposed to early life abuse or neglect, trying to get a comprehensive picture of different symptoms that might contribute to later psychopathology.</p>

Adenosine (A) to inosine (I) RNA editing is a widespread post-transcriptional mechanism in mammals that contributes to increase the protein diversity. Adenosine deaminases that act on RNA (ADARs) are the enzymes catalyzing RNA editing. ADARs are particularly active within the brain where they act on transcripts involved in neurotransmission. In this work the editing efficiency of all known site-selectively edited substrates have been analyzed during development of the mouse brain. We show that there is a global regulation of RNA editing, where editing levels of sites increase as the brain matures. This increase in editing efficiency cannot be explained by an increase in ADAR protein expression. During differentiation of primary cells from the mouse brain, editing levels increases similar to what we observe in vivo. Interestingly, the subcellular localization of the ADAR enzymes of cultured neurons show a different distribution in immature compared mature neurons. An accumulation of the ADAR enzymes in the nucleus may explain elevated A-to-I editing during brain development. Furthermore, we find that certain adenosines work as principal sites where editing of the transcript is initiated. Presumably, these sites are kinetically favored and are hypothesized to recruit the ADAR enzymes to the RNA substrate. Editing is then coupled to sites located in multiples of 12 nucleotides from each other. Interestingly, these sites reside on the same side in the 3D helix structure. The Gabra-3 transcript is site-selectively edited at a single position changing an isoleucine codon for a methionine upon editing. Gabra-3 encodes the a3 subunit of the GABAA receptor. We show that receptors assembled with edited a3 are less stable at the cell surface than the non-edited a3. We propose that the amino acid change upon editing, could affect protein interactions important for trafficking and stability of the GABAA receptors. Further, the editing event in a3 may have the function to reduce the number of a3 subunits in favor of other a subunits. / At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.

Several studies have shown that children who grow up under adverse care giving conditions are prone to develop a broad spectrum of different problems, ranging from mild depression to severe psychosomatic pathology later in life. A carefully treated child develops a different attachment strategy and biochemical response than a maltreated child. Early adverse events seem to program the stress response to become either over or under reactive which in turn have the potential to alter brain development. Major consequences include reduced plasticity and abnormal frontal lobe activity. This review further investigates the emotional and cognitive development in children exposed to early life abuse or neglect, trying to get a comprehensive picture of different symptoms that might contribute to later psychopathology.

Functional magnetic resonance imaging (fMRI) enables non-invasive investigation of the neural functions with excellent spatial resolution. Although fMRI has primarily been developed in young adult populations, its use is becoming widespread in paediatrics. However, there are many differences, both behavioural and physical, between adults and children requiring adjustments to imaging and analysis methodology to optimise the results in children. This thesis examines fMRI analysis methodology to improve the detection of developmental changes in the brain. The work uses an emotional and familiar face paradigm that elicits strong BOLD fMRI responses in the fusiform, a region that is still developing across childhood. This face paradigm also enables the comparison of the fusiform responses to the primary visual cortex to link to extensive results in the literature. Thirty five 4-8 year old children and fourteen adults (18-30 years old) were scanned. To address the concern of anatomical size differences between the brains of adults and children, the anatomical variability of the fusiform was measured and the validity of stereotaxic transformation into an adult template was confirmed for the children. To investigate the effect of threshold settings between the adults and children, individual subject analyses of the peak activation location, estimated signal percent change and noise values were calculated using the general linear model (GLM). Similar functional peak locations between individuals were quantitatively selected using a novel application of the activation likelihood estimation (ALE). Also, several different preprocessing steps were evaluated for their ability to correct for the increased motion frequently seen in children, in a quantitative framework (NPAIRS) using canonical variates analysis (CVA), a data driven multivariate model as well as the standard univariate GLM. Functional differences between the adults and the children were identified in the fusiform by applying these optimised procedures. The results of this thesis demonstrate that thresholding and preprocessing pipelines must be made in a group-specific fashion. These methods can also be extended to elderly populations, enabling the investigation of the complete ageing spectrum with fMRI.

Functional magnetic resonance imaging (fMRI) enables non-invasive investigation of the neural functions with excellent spatial resolution. Although fMRI has primarily been developed in young adult populations, its use is becoming widespread in paediatrics. However, there are many differences, both behavioural and physical, between adults and children requiring adjustments to imaging and analysis methodology to optimise the results in children. This thesis examines fMRI analysis methodology to improve the detection of developmental changes in the brain. The work uses an emotional and familiar face paradigm that elicits strong BOLD fMRI responses in the fusiform, a region that is still developing across childhood. This face paradigm also enables the comparison of the fusiform responses to the primary visual cortex to link to extensive results in the literature. Thirty five 4-8 year old children and fourteen adults (18-30 years old) were scanned. To address the concern of anatomical size differences between the brains of adults and children, the anatomical variability of the fusiform was measured and the validity of stereotaxic transformation into an adult template was confirmed for the children. To investigate the effect of threshold settings between the adults and children, individual subject analyses of the peak activation location, estimated signal percent change and noise values were calculated using the general linear model (GLM). Similar functional peak locations between individuals were quantitatively selected using a novel application of the activation likelihood estimation (ALE). Also, several different preprocessing steps were evaluated for their ability to correct for the increased motion frequently seen in children, in a quantitative framework (NPAIRS) using canonical variates analysis (CVA), a data driven multivariate model as well as the standard univariate GLM. Functional differences between the adults and the children were identified in the fusiform by applying these optimised procedures. The results of this thesis demonstrate that thresholding and preprocessing pipelines must be made in a group-specific fashion. These methods can also be extended to elderly populations, enabling the investigation of the complete ageing spectrum with fMRI.

While the genetics of retinoblastoma and the implications of the retinoblastoma susceptibility gene, RB1, are well described, there is still scarce evidence to suggest why RB1 acts in such a cell-type specific manner. Using the murine cortex as a model, we examined the effects of RB1 deletion of cycling neural progenitors and post-mitotic neurons, in order to ascertain cell-type specific functions in the central nervous system. Using the previously identified cell-cycle independent role for Rb in tangential migration, we validated Rb/E2f regulation of neogenin and implicated it in this process. In quiescent cortical neurons, we identified a pivotal role for Rb in neuronal survival. Unlike in cycling progenitors, in post-mitotic neurons Rb specifically represses the expression of cell-cycle associated genes in an E2f-dependent manner. Finally, in cortical neurons in the absence of Rb, we observe an activation of chromatin at E2f associated promoters. To determine the role of direct interaction between Rb and chromatin modifying enzymes, we utilized an acute LXCXE-binding deficient mutant paradigm. We report that the LXCXE binding motif is dispensable in establishment and maintenance of cortical neuron quiescence and survival. The activation state of E2f-responsive promoters appears to be dependent on E2f-activity and not simply Rb-mediated repression. Taken as a whole, this thesis serves to support the hypothesis that Rb plays a diverse role in different cell-types by regulation of unique gene targets and regulatory mechanisms. Characterizing specific cancer-initiating populations and understanding the specific function of Rb will help in the treatment of many cancers resulting from RB1 mutation or mutation within the Rb/E2f pathway.

The main aim of this thesis was to assess if early deprivation (ED) and glucocorticoid (GC) treatment exert long-term effects on the volume of the brain regions implicated in responses to stress, and if it associates with alterations in the distribution and structure of astroglia, which are known to support brain plasticity. This study also investigated the effects of prenatal dexamethasone (Dex) treatment on selected brain receptors, namely the oxytocin and 5-HT1A receptors, as they are implicated in the regulation of responses to stress. In addition, in vitro effects of Dex on neural stem cells were studied, in order to explore the drug effects on cell proliferation and differentiation, and on glial cell markers. Unbiased stereological estimation was employed to determine the regional brain volume, astroglial morphology and total cell count. Peripheral quantitative computed tomography (pQCT) technique was used to quantify total brain volume. Autoradiography technique was employed to visualise and analyse oxytocin and 5HT-1A serotonin receptor binding using selective radioactive ligands. The results of the present study demonstrate that both ED and prenatal Dex exposure leads to long-term effects on hippocampal remodelling with volume losses and impoverished astroglial morphology in the form of reduced primary process length. The observed deterioration in astroglial morphology adds further evidence that astrocytic changes contribute to hippocampal volume losses, a phenomenon that deserves more research in the context of effects of corticosteroid overload and stress-related pathologies. The present results also demonstrate that prenatal Dex induces long-term effects at the level of central neuroregulatory processes. Thus significant region- and sex-dependent reductions or increases in the oxytocin and 5-HT1A receptor binding were observed. The in vitro study has shown that Dex affects both proliferation and differentiation of GFAP positive NSCs with no toxic effects as such. Overall, both early postnatal or prenatal manipulations that increase levels of stress and/or glucocorticoids as the chemical mediators of stress, lead to a long-term maladaptive brain remodelling with losses in the hippocampal volume, impoverishment of hippocampal astroglial morphology and changes in the properties of central regulatory receptors in the brain areas involved in the reaction to stress.

Digoxin has been known as a treatment for chronic heart failure for over 200 years. Its effect on the heart itself has been extensively studied and its inotropic effect well established. The inotropic effect of digoxin is the result of its inhibition of the membrane sodium pump or Na+/K+-ATPase, which plays an important role in maintaining the resting membrane potential across the plasma membrane through constantly pumping Na+ and K+ across the plasma membrane. Na+/K+-ATPase is not found exclusively in heart muscle. It is also found extensively throughout the brain. As digoxin is the drug of choice for pregnant woman with chronic heart failure, this study aimed to examine how digoxin affects brain development and neurons in culture. The well established chicken embryo animal model was used in this study. To probe for deviations from normal brain development, chicken embryos were exposed in ovo. Brains were examined using both transmission and scanning electron microscopy. Microscopy indicated significant damage to the neurons, specifically membranes and mitochondria, as well as cellular death by means of aponecrosis. An unexpected result was premature myelinogenesis in the brain. Chick embryo neurons (CEN) were exposed to digoxin in vitro and cell viability was assessed by performing crystal violet (CV) assays. Results showed that cell number increased over time. This is however, impossible as CEN are non-dividing cells and results were therefore interpreted as an increase in protein synthesis over time, correlating with the myelinogenesis results seen with electron microscopy. To assess membrane integrity, fluorescence microscopy was performed using propidium iodide as stain. Results from this experiment showed a sharp increase in propidium iodide uptake in exposed cells indicative of the membrane damage caused by digoxin. These results also correlated with the aponecrosis seen with electron microscopy, as the nuclei indicated apoptosis while propidium iodide is normally only absorbed by cells undergoing necrosis. Finally, a literature search was conducted to shed some light on the role that digoxin plays in serotonin production and levels in the brain. From the literature it seems that digoxin could increase serotonin production and elevate serotonin levels in the brain, which may influence normal brain development and may therefore play a role in myelinogenesis in the brain. / Dissertation (MSc (Anatomy))--University of Pretoria, 2008. / Anatomy / unrestricted

While the genetics of retinoblastoma and the implications of the retinoblastoma susceptibility gene, RB1, are well described, there is still scarce evidence to suggest why RB1 acts in such a cell-type specific manner. Using the murine cortex as a model, we examined the effects of RB1 deletion of cycling neural progenitors and post-mitotic neurons, in order to ascertain cell-type specific functions in the central nervous system. Using the previously identified cell-cycle independent role for Rb in tangential migration, we validated Rb/E2f regulation of neogenin and implicated it in this process. In quiescent cortical neurons, we identified a pivotal role for Rb in neuronal survival. Unlike in cycling progenitors, in post-mitotic neurons Rb specifically represses the expression of cell-cycle associated genes in an E2f-dependent manner. Finally, in cortical neurons in the absence of Rb, we observe an activation of chromatin at E2f associated promoters. To determine the role of direct interaction between Rb and chromatin modifying enzymes, we utilized an acute LXCXE-binding deficient mutant paradigm. We report that the LXCXE binding motif is dispensable in establishment and maintenance of cortical neuron quiescence and survival. The activation state of E2f-responsive promoters appears to be dependent on E2f-activity and not simply Rb-mediated repression. Taken as a whole, this thesis serves to support the hypothesis that Rb plays a diverse role in different cell-types by regulation of unique gene targets and regulatory mechanisms. Characterizing specific cancer-initiating populations and understanding the specific function of Rb will help in the treatment of many cancers resulting from RB1 mutation or mutation within the Rb/E2f pathway.