Neurogenesis and neuronal differentiation in the postnatal frontal cortex in Down syndrome.

Although Down syndrome (DS), the most common developmental genetic cause of intellectual disability, displays proliferation and migration deficits in the prenatal frontal cortex (FC), a knowledge gap exists on the effects of trisomy 21 upon postnatal cortical development. Here, we examined cortical neurogenesis and differentiation in the FC supragranular (SG, II/III) and infragranular (IG, V/VI) layers applying antibodies to doublecortin (DCX), non-phosphorylated heavy-molecular neurofilament protein (NHF, SMI-32), calbindin D-28K (Calb), calretinin (Calr), and parvalbumin (Parv), as well as β-amyloid (APP/Aβ and Aβ) and phospho-tau (CP13 and PHF-1) in autopsy tissue from age-matched DS and neurotypical (NTD) subjects ranging from 28-weeks (wk)-gestation to 3 years of age. Thionin, which stains Nissl substance, revealed disorganized cortical cellular lamination including a delayed appearance of pyramidal cells until 44 wk of age in DS compared to 28 wk in NTD.

Postnatal Cytoarchitecture and Neurochemical Hippocampal Dysfunction in Down Syndrome.

Although the prenatal hippocampus displays deficits in cellular proliferation/migration and volume, which are later associated with memory deficits, little is known about the effects of trisomy 21 on postnatal hippocampal cellular development in Down syndrome (DS). We examined postnatal hippocampal neuronal profiles from autopsies of DS and neurotypical (NTD) neonates born at 38-weeks'-gestation up to children 3 years of age using antibodies against non-phosphorylated (SMI-32) and phosphorylated (SMI-34) neurofilament, calbindin D- (Calb), calretinin (Calr), parvalbumin (Parv), doublecortin (DCX) and Ki-67, as well as amyloid precursor protein (APP), amyloid beta (Aβ) and phosphorylated tau (p-tau). Although the distribution of SMI-32-immunoreactive (-ir) hippocampal neurons was similar at all ages in both groups, pyramidal cell apical and basal dendrites were intensely stained in NTD cases.