Increased RNA levels of the 25 kDa synaptosomal associated protein in brain samples of adult patients with Down Syndrome.
The synaptosomal associated protein of 25kDa (SNAP-25) is widely distributed in the brain and reduced in neurodegenerative diseases. In a previous paper we have shown reduced amounts of SNAP-25 protein in adult Down Syndrome (DS) brain. Neuronal cell death and downregulation at the transcriptional level may be responsible for the decrease. Therefore SNAP-25 mRNA levels were determined in frontal cortex and cerebellum of adult DS by a competitive reverse transcription-polymerase chain reaction. We found significantly increased mRNA levels in DS either related to 10 ng total RNA (P < 0.05 level in cerebellum: DS 2622 +/- 1081 attogr mean +/- SEM and controls 154 +/- 37 attogr. mean +/- SEM) or normalized versus the house keeping gene beta-actin (P < 0.05 level in frontal cortex: DS 1324 +/- 504 attogr. mean +/- SEM and control 131 +/- 32 attogr. mean +/- SEM; P<0.01 in cerebellum: DS 632 +/- 189 attogr. mean +/- SEM and control 21 +/- 2 attogr. mean +/- SEM). The main finding of this study shows elevated mRNA levels of SNAP-25 in adult DS brain whereas histological and protein-chemical evidence for decreased synaptosomal structures including SNAP-25 in a comparable cohort has been reported. We suggest compensatory mechanisms for the upregulation at the transcriptional level. We propose that SNAP-25 as many other brain proteins are regulated by protein stability rather than at the mRNA level.
Greber-Platzer
Susanne
S
Department of Pediatrics, University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. susanne.greber-platzer@akh-wien.ac.at
Fleischmann
Christine
C
Nussbaumer
Christa
C
Cairns
Nigel
N
Lubec
Gert
G
D002531:Cerebellum / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012313:RNA / Q000032:analysis* / Q000235:genetics; D012016:Reference Values; D050825:Synaptosomal-Associated Protein 25; D014158:Transcription, Genetic
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C494208:SNAP25 protein, human; D050825:Synaptosomal-Associated Protein 25; D012313:RNA