Evidence for apoptosis in the fetal Down syndrome brain.
In Down syndrome, enhanced apoptosis (programmed cell death) may play a role in the pathogenesis of characteristic early mental retardation and precocious neurodegeneration of Alzheimer type. Various apoptosis-associated proteins (Bax, Bcl-2, Fas, p53, Hsp70, neuronal apoptosis inhibitory protein-like immunoreactivity) were investigated in four different cortical regions and the cerebellum of one fetal Down syndrome (35 weeks' gestation) postmortem brain sample compared with a control brain sample. The most impressive finding was an at least fivefold elevation of Bax protein together with decreased Bcl-2 values in all Down syndrome cerebral regions investigated. In addition, antiapoptotic, presumably caspase-inhibitory, principles like heat shock protein 70 and neuronal apoptosis inhibitory protein were also reduced. Whereas Fas protein, an important member of receptor-mediated apoptosis, was inconsistently altered, a rather surprising finding was reduced proapoptotic, regulatory protein p53 in four of five regions. The findings are in good agreement with the proposed role of the Bcl-2 protein family in regulating developmental (naturally occurring) apoptotic neuronal death and further suggest that developmental apoptosis may be inappropriately commandeered by so far undefined pathologic processes in Down syndrome.
Seidl
R
R
Department of Pediatrics, University of Vienna, Austria.
Bidmon
B
B
Bajo
M
M
Yoo
P C
PC
Cairns
N
N
LaCasse
E C
EC
Lubec
G
G
D000025:Abortion, Eugenic; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D017209:Apoptosis / Q000235:genetics*; D001921:Brain / Q000473:pathology; D004314:Down Syndrome / Q000235:genetics* / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005819:Genetic Markers / Q000235:genetics*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D009419:Nerve Tissue Proteins / Q000235:genetics; D051616:Neuronal Apoptosis-Inhibitory Protein; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000235:genetics
C494826:BAX protein, human; D005819:Genetic Markers; D018840:HSP70 Heat-Shock Proteins; C496800:NAIP protein, human; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019014:fas Receptor