Total Numbers of Neurons and Glial Cells in Cortex and Basal Ganglia of Aged Brains with Down Syndrome--A Stereological Study

Abstract

The total numbers of neurons and glial cells in the neocortex and basal ganglia in adults with Down syndrome (DS) were estimated with design-based stereological methods, providing quantitative data on brains affected by delayed development and accelerated aging. Cell numbers, volume of regions, and densities of neurons and glial cell subtypes were estimated in brains from 4 female DS subjects (mean age 66 years) and 6 female controls (mean age 70 years). The DS subjects were estimated to have about 40% fewer neocortical neurons in total (11.1 × 10(9) vs. 17.8 × 10(9), 2p ≤ 0.001) and almost 30% fewer neocortical glial cells with no overlap to controls (12.8 × 10(9) vs. 18.2 × 10(9), 2p = 0.004). In contrast, the total number of neurons in the basal ganglia was the same in the 2 groups, whereas the number of oligodendrocytes in the basal ganglia was reduced by almost 50% in DS (405 × 10(6) vs. 816 × 10(6), 2p = 0.01). We conclude that trisomy 21 affects cortical structures more than central gray matter emphasizing the differential impairment of brain development. Despite concomitant Alzheimer-like pathology, the neurodegenerative outcome in a DS brain deviates from common Alzheimer disease.

A stereological study of the mediodorsal thalamic nucleus in Down syndrome

“…These deficiencies are associated with structural and neurochemical alterations in higher anatomical regions such as the hippocampal formation and prefrontal cortex (PFC). In a previous study, we reported that cortical regions in brains from aged subjects with DS were significantly smaller when compared to agematched controls in terms of cell numbers, volume, and surface areas, but not cortical thickness (Karlsen and Pakkenberg, 2011). The reduced brain volume and cell numbers are likely caused by delayed cerebral development due to changes in cell cycle kinetics.…”

“…The same DS brains were used in a previous stereological study (Karlsen and Pakkenberg, 2011) and the data will indicate if the large decrease in neurons in the frontal cortex of patients with DS is reflected in the number of neurons of the MDT nucleus. …”

Structural brain alterations of Down’s syndrome in early childhood evaluation by DTI and volumetric analyses

“…A reduced cortical GM volume may reflect the post-mortem findings of simplified gyral patterns, decreased neuronal density, lamination [28] and reduction of about 30-40 % in the number of both neurons and glial cells [29]. This abnormal development of cortical neurons can lead to learning and memory problems or seizures that begin to emerge in late infancy.…”

“…Although a regional GM volume decline in the left putamen, bilateral thalamus and caudate nucleus as well as the brain stem represents initial data in volumetric neuroimaging studies of DS, Anderson et al [30] reported involvement of these structures with functional MR imaging (fmri) and Karlsen et al [29] showed there were about 40 % fewer neurons in the thalami of DS brains compared to control brains. Gating sensory input from the brainstem and sensory areas to the cortex and other subcortical regions leads the thalamus and basal ganglia to act as key components for integrating cognition and affective experience.…”

Causal Mathematical Logic as a guiding framework for the prediction of “Intelligence Signals” in brain simulations

“…Recent experiments implanted the more complex human astrocytes in rodents resulting in increases to their memory (Han et al, 2013). Pre-existing data had already proposed a correlation between astrocyte to neuron ratio, cortical surface gyration (Eriksen and Pakkenberg, 2007) and intelligence (Sherwood et al, 2006;Karlsen and Pakkenberg 2011;Marino et al, 2007).…”