Miwa Takashima, Seiichiro Takahashi, Osuke Iwata, Sachiko Iwata, Masahiro Yokoo and Sachio Takashima
Background: The aim of the study was to clarify the developmental and aging changes of Protein gene product 9.5 (PGP9.5) expression in granular and pyramidal neurons of the cerebral cortex comparing patients with Down syndrome (DS) and subjects without it.
Subjects and Methods: Fifty-four human brains were obtained from post-mortem samples of 24 subjects with DS (19 weeks gestation (GW) to 63 years of age) and 30 subjects without it (20 GW to 75 years of age). PGP9.5 expression in the frontal cerebri was qualitatively assessed in specific cortical layers and compared among 4 age groups (fetus, infant, child, and adult), and between the brains with and without DS.
Results: In subjects without DS, the expression of PGP9.5 in the cerebral cortex was highest from 30 to 39 GW, and then decreased with increasing age. In patients with DS, cortical PGP9.5 expression did not decrease with aging. Compared with samples from subjects without DS, those from patients with DS showed weaker PGP9.5 expression in layers 3 and 5 (pyramidal cell layers) of the infant group, but stronger expression in layer 4 (granule cell layer) of the child group, and in layers 2, 3, 4, and 6 of the adult group.
Conclusion: An increase of PGP9.5 expression in cortical granule neurons from children to adults with DS was found and suggests the existence of an important therapeutic window during which compensatory and plastic processes may influence the progression of cognitive impairment in individuals with DS.
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