Dendritic and histochemical development and ageing in patients with Down's syndrome

Abstract

ABSTRACT. Mental retardation and dementia characteristic of Down's syndrome (DS) have a complex pathogenesis. Golgi and immunohistochemical studies were done on DS patients and controls from foetuses and elderly adults. Golgi studies on the cerebral cortex revealed that the postsynaptic spines on the basal dendrites increase from neonate to 15 years of age and gradually decrease after 20 years in controls, but poorly increase in children and rapidly decrease in adults with DS. This deficient synaptogenesis and dendritic atrophy may be related to mental retardation. On the other hand, immunohistochem‐istry on proteins, whose genes are located on chromosome 21, revealed that c‐temiinal protein of beta‐amyloid appears in neurons of DS, S‐100‐positive glia increases in the hippocampus of neonates and adults, and membrane protein OK‐2 is expressed earlier and is more widespread in the DS brains. The overexpression and early appearance of gene products in DS brains may be related to the pathogenesis of or predisposition to mental disorders or to dendritic hypogenesis.

Trisomy-driven overexpression of DYRK1A kinase in the brain of subjects with Down syndrome

“…This could be the reflection of well-documented delay in development of DS infants [3,18,24,26], particularly in dendritization process, in which DYRK1A has been shown to be involved. [13,27].…”

Cranial irradiation compromises neuronal architecture in the hippocampus

“…Alterations in the geometry and branching pattern of the dendritic tree can be profound, and are often accompanied by severe cognitive disorders that impact learning and memory (14)(15)(16). Reductions in dendritic complexity are observed in many brain disorders, such as epilepsy (17), recurrent depressive illness (18), Alzheimer's disease (19), and Huntington disease (20), and dendritic abnormalities exhibit strong correlations with mental retardation found in Down syndrome (21), Rett syndrome (22), and Fragile-X syndromes (20). Thus, it is not surprising that the functional integrity of the CNS is directly related to neuronal morphology, as the proper growth and arborization of dendrites are crucial for cognitive health (15).…”

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“…The gene for S100B is located on human chromosome 21 [7]. The relationship of S100 to human brain disorders is supported by the finding that there is an increase in the level of S100B in the amniotic fluid in trisomy-21 fetuses [8], the number of glial cells expressing S100B is increased in patients with trisomy 21 (Down's syndrome) [9,10] as well as in patients with certain forms of Alzheimer's disease [11,12] associated with similar genetic defects on chromosome 21. Most of the S100 proteins identified on human chromosome 1 have been named using S100A plus a number to identify its location on chromosome 1 (e.g., S100A1, S100A2, etc.).…”

“…S100 proteins have been implicated as modulators of Ca 2+ -dependent processes, such as secretion/neurotransmission [19][20][21] and intracellular Ca 2+ release [22]. In addition, S100 proteins, in particular S100B, may be related to tissue development, repair and regeneration [23], the process of learning and memory [24] and appear to play a role in central nervous system development and pathologies [9][10][11][12]. In addition to Down's syndrome and Alzheimer's disease, S100B is also over expressed in children with cerebral palsy [25] and has been implicated in schizophrenia [26] and affective disorders [27].…”