PMID- 19835666
OWN - NLM
STAT- MEDLINE
DCOM- 20100624
LR  - 20161020
IS  - 1469-5111 (Electronic)
IS  - 1461-1457 (Linking)
VI  - 13
IP  - 3
DP  - 2010 Apr
TI  - Autoantibodies from schizophrenia patients induce cerebral cox-1/iNOS mRNA 
      expression with NO/PGE2/MMP-3 production.
PG  - 293-303
LID - 10.1017/S1461145709990770 [doi]
AB  - We demonstrated that circulating antibodies from schizophrenia patients, which 
      interact with cerebral M1 muscarinic acetylcholine receptors (M1 mAChRs), trigger 
      production of nitric oxide (NO), prostaglandin E2 (PGE2) and matrix 
      metalloproteinase-3 (MMP-3), and act as inducers of cyclooxygenase-1 (cox-1) and 
      inducible nitric oxide synthase (iNOS) mRNA expression in the rat frontal cortex. 
      The corresponding affinity-purified anti-M1 peptide IgG from schizophrenia 
      patients, while stimulating cerebral M1 mAChRs, increases NOS activity, PGE2 and 
      MMP-3 production associated with iNOS over-activity and mRNA expression. 
      Moreover, PGE2 and MMP-3 production is the result of cox-1 expression and 
      activity. All these effects were inhibited by pirenzepine or haloperidol and 
      mimicked the action of the authentic mAChR agonist. Concurrent analysis of the 
      effects of iNOS, phospholipase C, protein kinase C and calcium/calmodulin 
      inhibition showed that antibody up-regulation of NOS activity, PGE2 and MMP-3 
      production is under the control of the endogenous NO signalling system. These 
      results provide evidence of the role that cholinergic receptor antibodies play in 
      the development of cerebral inflammation, which shows that an antibody that 
      interacts with cerebral mAChRs can induce expression of pro-inflammatory 
      mediators, and support the participation of an autoimmune process in a particular 
      group of chronic schizophrenia patients.
FAU - Ganzinelli, Sabrina
AU  - Ganzinelli S
AD  - Pharmacology Unit, School of Dentistry, University of Buenos Aires and Argentine 
      National Research Council (CONICET), Buenos Aires, Argentina.
FAU - Borda, Enri
AU  - Borda E
FAU - Sterin-Borda, Leonor
AU  - Sterin-Borda L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091019
PL  - England
TA  - Int J Neuropsychopharmacol
JT  - The international journal of neuropsychopharmacology
JID - 9815893
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Autoantibodies)
RN  - 0 (Membrane Proteins)
RN  - 0 (Peptides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Muscarinic M1)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.99.1 (Cyclooxygenase 1)
RN  - EC 1.14.99.1 (Ptgs1 protein, rat)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Antipsychotic Agents/pharmacology
MH  - Autoantibodies/*pharmacology
MH  - Case-Control Studies
MH  - Cerebral Cortex/*drug effects
MH  - Cyclooxygenase 1/*genetics
MH  - Dinoprostone/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Male
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Membrane Proteins/*genetics
MH  - Middle Aged
MH  - Models, Biological
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Synthase Type II/*genetics
MH  - Peptides/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Muscarinic M1/immunology
MH  - Schizophrenia/blood/immunology
EDAT- 2009/10/20 06:00
MHDA- 2010/06/25 06:00
CRDT- 2009/10/20 06:00
PHST- 2009/10/20 06:00 [entrez]
PHST- 2009/10/20 06:00 [pubmed]
PHST- 2010/06/25 06:00 [medline]
AID - S1461145709990770 [pii]
AID - 10.1017/S1461145709990770 [doi]
PST - ppublish
SO  - Int J Neuropsychopharmacol. 2010 Apr;13(3):293-303. doi: 
      10.1017/S1461145709990770. Epub 2009 Oct 19.