Abnormalities of amount and function of presynaptic terminals may have an important role in the mechanism of illness in
schizophrenia. The
SNARE proteins (SNAP-25,
syntaxin, and VAMP) are enriched in presynaptic terminals, where they interact to form a functional complex to facilitate vesicle fusion.
SNARE protein amounts are altered in the cortical regions in
schizophrenia, but studies of
protein-
protein interactions are limited. We extended these investigations to the striatal regions (such as the nucleus accumbens, ventromedial caudate (VMC), and dorsal caudate) relevant to disease symptoms. In addition to measuring
SNARE protein levels, we studied
SNARE protein-
protein interactions using a novel ELISA method. The possible effect of
antipsychotic treatment was investigated in parallel in the striatum of rodents that were administered
haloperidol and
clozapine. In
schizophrenia samples, compared with controls, SNAP-25 was 32% lower (P=0.015) and
syntaxin was 26% lower (P=0.006) in the VMC. In contrast, in the same region,
SNARE protein-
protein interactions were higher in
schizophrenia (P=0.008). Confocal microscopy of
schizophrenia and control VMC showed qualitatively similar
SNARE protein immunostaining.
Haloperidol treatment of rats increased levels of SNAP-25 (mean 24%, P=0.003),
syntaxin (mean 18%, P=0.010), and VAMP (mean 16%, P=0.001), whereas
clozapine increased only the VAMP level (mean 13%, P=0.004). Neither
drug altered
SNARE protein-
protein interactions. These results indicate abnormalities of amount and interactions of
proteins directly related to presynaptic function in the VMC in
schizophrenia.
SNARE proteins and their interactions may be a novel target for the development of
therapeutics.