Evidence for apoptosis in the fetal Down syndrome brain

Topic: Brain proteins, microglia and lab models

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.

@article{seidl2001-11417611,
  author  = {Seidl, R. and Bidmon, B. and Bajo, M. and Yoo, P. C. and Cairns, N. and LaCasse, E. C. and Lubec, G.},
  title   = {{Evidence for apoptosis in the fetal Down syndrome brain}},
  journal = {Journal of child neurology},
  year    = {2001},
  doi     = {10.1177/088307380101600610},
  pmid    = {11417611},
  url     = {https://doi.org/10.1177/088307380101600610}
}

Key findings

• 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 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.

Why it matters

In a single fetal Down syndrome brain at 35 weeks' gestation, Bax protein was at least fivefold elevated and Bcl-2 was decreased across cerebral regions, with reduced heat shock protein 70 and neuronal apoptosis inhibitory protein. The authors suggest developmental apoptosis may be inappropriately activated in Down syndrome, but this is a single-sample study and does not test any treatment or cure.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1177/088307380101600610
• PubMed: 11417611
• Original source →

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