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Molecular evidence for decreased synaptic efficacy in the postmortem olfactory bulb of individuals with schizophrenia

Citation

Egbujo, CN and Sinclair, D and Borgmann-Winter, KE and Arnold, SE and Turetsky, BI and Hahn, C-G, Molecular evidence for decreased synaptic efficacy in the postmortem olfactory bulb of individuals with schizophrenia, Schizophrenia Research, 168, (1-2) pp. 554-562. ISSN 0920-9964 (2015) [Refereed Article]

Copyright Statement

Copyright 2015 Elsevier B.V.

DOI: doi:10.1016/j.schres.2015.07.026

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.

Item Details

Item Type:Refereed Article
Keywords:synapse, schizophrenia
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
UTAS Author:Sinclair, D (Dr Duncan Sinclair)
ID Code:130629
Year Published:2015
Web of Science® Times Cited:9
Deposited By:Wicking Dementia Research and Education Centre
Deposited On:2019-02-06
Last Modified:2019-04-08
Downloads:0

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