Down syndrome (DS) is a common genetic developmental disorder characterized by the trisomy of chromosome 21 (Hsa21). All individuals with DS have some kind of intellectual disability, associated with dysfunction in cognition-related structures, including the frontal cortex. Studies have examined developmental changes in the frontal cortex during prenatal stages in DS, however little is known about cortical lamination and neuronal differentiation in postnatal periods in this neurodevelopmental disorder. Therefore, we examined the quantitative and qualitative distribution of neuronal profiles containing the neuronal migration protein doublecortin (DCX), the non-phosphorylated high-molecular-weight neurofilament SMI-32, the calcium-binding proteins calbindin D-28K (Calb), calretinin (Calr), and parvalbumin (Parv), as well as human β-amyloid and APP (6E10), Aβ1-42, and phospho-tau (CP-13) in the supragranular (SG, II/III) and infragranular (IG, V/VI) layers in the DS postnatal frontal cortex compared to neurotypically developing (NTD) controls from ages 28 weeks to 196.4 weeks using immunohistochemistry. Furthermore, cortical lamination was evaluated using thionin, a Nissl stain. We found DCX-immunoreactive (-ir) cells in both the SG and IG layers in younger cases, but not in the oldest cases in both groups. Strong expression of SMI-32 immunoreactivity was observed in pyramidal cells in layers III and V in the oldest cases in both groups, however SMI-32-ir cells appeared much earlier in NTD compared to DS. We found small and fusiform Calb-ir cells in the younger cases (28 to 44 weeks), while in the oldest cases, Calb immunoreactivity was also found in pyramidal cells. Calr-ir cells appeared earlier in DS at 32 weeks compared to NTD at 44 weeks, however both groups showed large bipolar fusiform-shaped Calr-ir cells in the oldest cases. Diffuse APP/Aβ-ir plaque-like accumulations were found in the frontal cortex grey and white matter at all ages, but no Aβ1-42 immunoreactivity was detected in any case. Furthermore, neuropil (but not cellular) granular CP-13 immunostaining was seen in layer I only at 41 weeks NTD and 33 weeks DS. Cell counts show a significantly higher cell number in SG compared to IG for all the neuronal markers in both groups, except in Calb and SMI-32. In NTD, age and brain weight showed the strongest correlations with all cellular counts, except in thionin where DS had a stronger negative correlation with age and brain weight compared to NTD. In addition, height and body weight showed a strong negative correlation in NTD with the migration and neurogenesis marker DCX. These findings suggest that trisomy 21 affects the postnatal frontal cortex lamination, neuronal migration<br/>eurogenesis, and differentiation of projection pyramidal cells and interneurons, which contribute to the disruption of the local and projection inhibitory and excitatory circuitries that may underlie the cognitive disabilities in DS.

The purpose of this study was to examine the validity of a modified Assisted Cycling Therapy bicycle for improving depression in children with Down Syndrome (DS). Seven participants completed 2x/week for 8 weeks, 30 minutes at a time of ACT, in which participants’ voluntary pedaling rates were augmented via the bicycle motor, ensuring that they were pedaling at a rate greater than their self-paced rate. Depression was measured using a modified version of the Children’s Depressive Inventory, called the CDI-2. Our study demonstrated that the scores from the CDI-2 decreased, demonstrating less depressive symptomatology after the conclusion of the 8 week intervention. Our results were interpreted via our model of the mechanisms involved in influencing the success of ACT. Future research would include a greater sample size, a more relevant measure of depressive scores, and a consistent data collection environment. However our initial pilot study showed promising results for improving mental health in children with DS.

The primary goal of this study is to assess and develop an understanding of the effects of Assisted Cycling Therapy on manual motor performance in children with Down syndrome. Seven children (Mage 11.6 years old) completed a 30-minute cycle session 2x/week for 8 weeks on the PACT bicycle at a 35% greater rate than their self-selected rate. Pre- and post-testing of grip force with a dynamometer and unimanual and bimanual manual dexterity using the Purdue Pegboard were measured to determine changes in force production and fine motor control, respectively. Results consistently showed improvements in grip force in both hands and bimanual dexterity following PACT. My results are interpreted with respect to cerebral lateralization and neuroplasticity following PACT intervention.