SNAP-25 genotype influences NAA/Cho in left hippocampus

Abstract

The SNAP-25 gene is an integral part of the vesicle docking and fusion machinery that controls neurotransmitter release. Several post mortem studies revealed a reduction of SNAP-25 protein in the hippocampus of patients with schizophrenia and bipolar disorder (BD). Thirty-eight patients with schizophrenia, BD or obsessivecompulsive disorder and 17 healthy controls participated in the study. Proton magnetic resonance spectroscopy in left hippocampus was performed in each individual. Three single nucleotide polymorphisms (SNP) of the SNAP-25 gene were genotyped. Individuals with the homozygous CC genotype of the DdeI SNP presented a significantly higher ratio of N-acetyl-aspartate (NAA)/choline-containing compounds (Cho) in the left hippocampus compared to the group of individuals with the homozygous TT genotype. The SNAP-25 genotype may modulate synaptic plasticity and neurogenesis in the left hippocampus, and altered NAA/Cho ratio may be an indicator for this genetic modulation of neuronal function in the hippocampus.

Network-Based Elucidation of Human Disease Similarities Reveals Common Functional Modules Enriched for Pluripotent Drug Targets

“…Decreased synaptic function has also been observed for both BIP and SCHZ [15],[16]. In particular, the levels of protein SNAP-25 was shown to be reduced in both BIP and SCHZ [17]. The function of this module in GLIO is still to be explored.…”

Magnetic resonance spectroscopy of limbic structures displays metabolite differences in young unaffected relatives of schizophrenia probands

“…Lower NAA in schizophrenia probands (and by extension their biological relatives) has been thought to be a marker for neurodevelopmental disruption in neuronal proliferation, and/or synaptic connectivity and neuroxonal myelin maintenance (Keshavan et al, 1997; Jessen et al, 2006). Furthermore, NAA/Cho levels in the left hippocampus are modulated by the SNAP-25 genotype (Scherk et al, 2008). The SNAP-25 protein is part of the neurotransmitter exocytosis machinery and is down-regulated in the post-mortem hippocampus in schizophrenia and bipolar disorder.…”

Association of the brain-derived neurotrophic factor val66met polymorphism with magnetic resonance spectroscopic markers in the human hippocampus: in vivo evidence for effects on the glutamate system

“…As described previously [39], single-volume 1 H-MRS was performed on a 1.5-Tesla Siemens Magnetom Sonata (Siemens, Erlangen) using a spin-echo sequence with water suppression and 128 scan averages (TE = 30, TR = 1.500). Regions of interest were defined in the left hippocampus, in the middle third of the left middle frontal gyrus (referred to as left dorsolateral prefrontal cortex), and in the left posterior frontomedian cortex along the cingulate sulcus.…”