title: Molecular evidence for decreased synaptic efficacy in the postmortem olfactory bulb of individuals with schizophrenia.
abstract: Multiple lines of evidence suggest altered synaptic plasticity/connectivity as a pathophysiologic mechanism for various symptom domains of schizophrenia. Olfactory dysfunction, an endophenotype of schizophrenia, reflects altered activity of the olfactory circuitry, which conveys signals from olfactory receptor neurons to the olfactory cortex via synaptic connections in the glomeruli of the olfactory bulb. The olfactory system begins with intranasal olfactory receptor neuron axons synapsing with mitral and tufted cells in the glomeruli of the olfactory bulb, which then convey signals directly to the olfactory cortex. We hypothesized that olfactory dysfunction in schizophrenia is associated with dysregulation of synaptic efficacy in the glomeruli of the olfactory bulb. To test this, we employed semi-quantitative immunohistochemistry to examine the olfactory bulbs of 13 postmortem samples from schizophrenia and their matched control pairs for glomerular expression of 5 pre- and postsynaptic proteins that are involved in the integrity and function of synapses. In the glomeruli of schizophrenia cases compared to their matched controls, we found significant decreases in three presynaptic proteins which play crucial roles in vesicular glutamate transport - synapsin IIa (-18.05%, p=0.019), synaptophysin (-24.08% p=0.0016) and SNAP-25 (-23.9%, p=0.046). Two postsynaptic proteins important for spine formation and glutamatergic signaling were also decreased-spinophilin (-17.40%, p=0.042) and PSD-95 (-34.06%, p=0.015). These findings provide molecular evidence for decreased efficacy of synapses within the olfactory bulb, which may represent a synaptic mechanism underlying olfactory dysfunction in schizophrenia.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Chijioke N
authors.initials: CN
authors.lastname: Egbujo
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Duncan
authors.initials: D
authors.lastname: Sinclair
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA; Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Karin E
authors.initials: KE
authors.lastname: Borgmann-Winter
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Bruce I
authors.initials: BI
authors.lastname: Turetsky
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: hahnc@mail.med.upenn.edu.
authors.forename: Chang-Gyu
authors.initials: CG
authors.lastname: Hahn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000627:therapeutic use; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009830:Olfactory Bulb / Q000378:metabolism* / Q000473:pathology*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D013569:Synapses / Q000378:metabolism* / Q000473:pathology*; D016704:Synapsins / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D000099273:Neurabins
chemical_list: D014150:Antipsychotic Agents; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D016704:Synapsins; D016708:Synaptophysin; D050825:Synaptosomal-Associated Protein 25; D000099273:Neurabins; C501444:DLG4 protein, human; C494208:SNAP25 protein, human; C000604872:SYN2 protein, human; C569014:SYP protein, human
keywords: Olfactory bulb; PSD-95; SNAP-25; Schizophrenia; Synapse; Synaptophysin