Increased RNA levels of the 25 kDa synaptosomal associated protein in brain samples of adult patients with Down Syndrome

Abstract

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.