title: Changes in cholinergic and glutamatergic markers in the striatum from a sub-set of subjects with schizophrenia.
abstract: OBJECTIVE
  Having separated a sub-group of people with schizophrenia based on a marked loss of cortical [(3)H]pirenzepine binding (MRDS); we wished to determine if MRDS had lower levels of [(3)H]pirenzepine and other muscarinic receptor antagonist binding to the striatum and if this was due to loss of pre- or post-synaptic neurons or glia measured using surrogate markers (25 kilodalton synaptosomal-associated protein (SNAP 25), postsynaptic density protein 95 (PSD 95), glial fibrillary acidic protein (GFAP) 41/43) of cell number.
  
  
  METHODS
  [(3)H]pirenzepine, [(3)H]AF-DX 384 and [(3)H]4-DAMP binding to the striatum from 37 subjects with schizophrenia (19 MRDS) and 20 controls as well as SNAP 25, PSD 95 and GFAP 41/43 in crude particulate membrane were measured.
  
  
  RESULTS
  [(3)H]pirenzepine and [(3)H]AF-DX 384 binding to the striatum were significantly lower in schizophrenia due to lower binding of both radioligands in the striatum from MRDS. Levels of PSD 95 were higher in schizophrenia, predominantly due to higher levels in MRDS.
  
  
  CONCLUSIONS
  Our data suggest muscarinic M1 ([(3)H]pirenzepine) and M2 and/or M4 receptors ([(3)H]AF-DX 384) are lower in the striatum from MRDS which could mediate inappropriate adaption to internal and external cues which, in turn, would affect motivation, cognition and motor control. Increased levels of PSD 95 could indicate increased post-synaptic boutons or changes in NMDA receptor-mediated signalling in MRDS.
authors.affiliation: The Molecular Psychiatry Laboratories, The Florey Institute for Neuroscience and Mental Health, Parkville, Australia; The Department of Psychiatry, The University of Melbourne, Parkville, Australia. Electronic address: anddali@unimelb.edu.au.
authors.forename: Brian
authors.initials: B
authors.lastname: Dean
authors.affiliation: The Department of Psychiatry, The University of Melbourne, Parkville, Australia; The Molecular Psychiatry Laboratories, The Florey Institute for Neuroscience and Mental Health, Parkville, Australia.
authors.forename: Natalie
authors.initials: N
authors.lastname: Thomas
authors.affiliation: The Molecular Psychiatry Laboratories, The Florey Institute for Neuroscience and Mental Health, Parkville, Australia; The Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Genetic Epidemiologic Core, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chi-Yu
authors.initials: CY
authors.lastname: Lai
authors.affiliation: The Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Genetic Epidemiologic Core, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Wei J
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: The Department of Psychiatry, The University of Melbourne, Parkville, Australia; The Molecular Psychiatry Laboratories, The Florey Institute for Neuroscience and Mental Health, Parkville, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Scarr
mesh_terms: D001345:Autoradiography; D015153:Blotting, Western; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D018727:Muscarinic Antagonists; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010880:Piperidines; D010890:Pirenzepine / Q000031:analogs & derivatives; D011869:Radioligand Assay; D019275:Radiopharmaceuticals; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D014316:Tritium
chemical_list: C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D005904:Glial Fibrillary Acidic Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018727:Muscarinic Antagonists; D010880:Piperidines; D019275:Radiopharmaceuticals; D011976:Receptors, Muscarinic; C494208:SNAP25 protein, human; D050825:Synaptosomal-Associated Protein 25; D014316:Tritium; C065959:AFDX 384; D010890:Pirenzepine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium