HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

A novel mechanism and treatment target for presynaptic abnormalities in specific striatal regions in schizophrenia.

Abstract
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.
AuthorsVilte E Barakauskas, Clare L Beasley, Alasdair M Barr, Athena R Ypsilanti, Hong-Ying Li, Allen E Thornton, Hubert Wong, Gorazd Rosokilja, J John Mann, Branislav Mancevski, Zlatko Jakovski, Natasha Davceva, Boro Ilievski, Andrew J Dwork, Peter Falkai, William G Honer
JournalNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology) Vol. 35 Issue 5 Pg. 1226-38 (Apr 2010) ISSN: 1740-634X [Electronic] England
PMID20072114 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antipsychotic Agents
  • SNARE Proteins
  • Clozapine
  • Haloperidol
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antipsychotic Agents (pharmacology)
  • Clozapine (pharmacology)
  • Corpus Striatum (drug effects, metabolism)
  • Female
  • Haloperidol (pharmacology)
  • Humans
  • Male
  • Middle Aged
  • Presynaptic Terminals (drug effects, metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • SNARE Proteins (metabolism)
  • Schizophrenia (drug therapy, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: