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Assessment of radial glia in the frontal lobe of fetuses with Down syndrome.

ABSTRACT: Down syndrome (DS) occurs with triplication of human chromosome 21 and is associated with deviations in cortical development evidenced by simplified gyral appearance and reduced cortical surface area. Radial glia are neuronal and glial progenitors that also create a scaffolding structure essential for migrating neurons to reach cortical targets and therefore play a critical role in cortical development. The aim of this study was to characterise radial glial expression pattern and morphology in the frontal lobe of the developing human fetal brain with DS and age-matched controls. Secondly, we investigated whether microstructural information from in vivo magnetic resonance imaging (MRI) could reflect histological findings from human brain tissue samples. Immunohistochemistry was performed on paraffin-embedded human post-mortem brain tissue from nine fetuses and neonates with DS (15-39 gestational weeks (GW)) and nine euploid age-matched brains (18-39 GW). Radial glia markers CRYAB, HOPX, SOX2, GFAP and Vimentin were assessed in the Ventricular Zone, Subventricular Zone and Intermediate Zone. In vivo diffusion MRI was used to assess microstructure in these regions in one DS (21 GW) and one control (22 GW) fetal brain. We found a significant reduction in radial glial progenitor SOX2 and subtle deviations in radial glia expression (GFAP and Vimentin) prior to 24 GW in DS. In vivo, fetal MRI demonstrates underlying radial projections consistent with immunohistopathology. Radial glial alterations may contribute to the subsequent simplified gyral patterns and decreased cortical volumes observed in the DS brain. Recent advances in fetal MRI acquisition and analysis could provide non-invasive imaging-based biomarkers of early developmental deviations.

SUBMITTER: Baburamani AA

PROVIDER: S-EPMC7441567 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Assessment of radial glia in the frontal lobe of fetuses with Down syndrome.

Baburamani Ana A AA Vontell Regina T RT Uus Alena A Pietsch Maximilian M Patkee Prachi A PA Wyatt-Ashmead Jo J Chin-Smith Evonne C EC Supramaniam Veena G VG Donald Tournier J J Deprez Maria M Rutherford Mary A MA

Acta neuropathologica communications 20200820 1

Down syndrome (DS) occurs with triplication of human chromosome 21 and is associated with deviations in cortical development evidenced by simplified gyral appearance and reduced cortical surface area. Radial glia are neuronal and glial progenitors that also create a scaffolding structure essential for migrating neurons to reach cortical targets and therefore play a critical role in cortical development. The aim of this study was to characterise radial glial expression pattern and morphology in t ...[more]

PMID: 32819430

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Project description:Conceptualizations of the nature of acquired personality disturbances after brain damage, especially to prefrontal cortex, have progressed from clinical observations of a large, disparate set of disturbances to theories concerning neuroanatomically-based subgroups with prefrontal damage. However, hypothesized subtypes have not yet been studied systematically. Based on our previous investigations of acquired personality disturbances, we hypothesized five subtypes of acquired personality disturbances: Executive Disturbances, Disturbed Social Behavior, Emotional Dysregulation, Hypo-emotionality/De-Energization, and Distress, as well as an undisturbed group. Subtypes were investigated in 194 adults with chronic, stable, focal lesions located in various aspects of prefrontal lobes and elsewhere in the brain, using two different cluster analysis techniques applied to ratings on the Iowa Scales of Personality Change. One technique was a hypothesis-driven approach; the other was a set of strictly empirical analyses to assess the robustness of clusters found in the first analysis. The hypothesis-driven analysis largely supported the hypothesized set of subtypes. However, in contrast to the hypothesis, it suggested that disturbed social behavior and emotional dysregulation are not two distinct subtypes, but two aspects of one multifaceted type of disturbance. Additionally, the so-labeled "executive disturbances" group also showed disturbances in other domains. Results from the second (empirical) set of cluster analyses were consistent with findings from the hypothesis-driven cluster analysis. Overall, findings across the two cluster analyses indicated four subtypes of acquired personality disturbances: (1) executive disturbances in association with generalized disturbance, (2) dysregulation of emotions and behavior, (3) hypo-emotionality and de-energization, and (4) distress/anxiety. These findings show strong correspondence with subtypes suggested by prominent models of prefrontal systems based on neuroanatomically-defined circuits. Clarification of distinctive subtypes of acquired personality disturbances is a step toward enhancing our ability to tailor rehabilitative interventions for patients with prefrontal brain injuries.

Dataset Information

Assessment of radial glia in the frontal lobe of fetuses with Down syndrome.

Publications

Assessment of radial glia in the frontal lobe of fetuses with Down syndrome.

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