Molecular evidence of synaptic pathology in the CA1 region in schizophrenia

Journal article


Matosin, Natalie, Fernandez-Enright, Francesca, Lum, Jeremy S., Engel, Martin, Andrews, Jessica L., Gassen, Nils C., Wagner, Klaus V., Schmidt, Mathias V. and Newell, Kelly A.. (2016). Molecular evidence of synaptic pathology in the CA1 region in schizophrenia. Schizophrenia. 2(16022), pp. 1 - 8. https://doi.org/10.1038/npjschz.2016.22
AuthorsMatosin, Natalie, Fernandez-Enright, Francesca, Lum, Jeremy S., Engel, Martin, Andrews, Jessica L., Gassen, Nils C., Wagner, Klaus V., Schmidt, Mathias V. and Newell, Kelly A.
Abstract

Alterations of postsynaptic density (PSD)95-complex proteins in schizophrenia ostensibly induce deficits in synaptic plasticity, the molecular process underlying cognitive functions. Although some PSD95-complex proteins have been previously examined in the hippocampus in schizophrenia, the status of other equally important molecules is unclear. This is especially true in the cornu ammonis (CA)1 hippocampal subfield, a region that is critically involved in the pathophysiology of the illness. We thus performed a quantitative immunoblot experiment to examine PSD95 and several of its associated proteins in the CA1 region, using post mortem brain samples derived from schizophrenia subjects with age-, sex-, and post mortem interval-matched controls (n = 20/group). Our results indicate a substantial reduction in PSD95 protein expression (−61.8%). Further analysis showed additional alterations to the scaffold protein Homer1 (Homer1a: +42.9%, Homer1b/c: − 24.6%), with a twofold reduction in the ratio of Homer1b/c:Homer1a isoforms (P = 0.011). Metabotropic glutamate receptor 1 (mGluR1) protein levels were significantly reduced (−32.7%), and Preso, a protein that supports interactions between Homer1 or PSD95 with mGluR1, was elevated (+83.3%). Significant reduction in synaptophysin (−27.8%) was also detected, which is a validated marker of synaptic density. These findings support the presence of extensive molecular abnormalities to PSD95 and several of its associated proteins in the CA1 region in schizophrenia, offering a small but significant step toward understanding how proteins in the PSD are altered in the schizophrenia brain, and their relevance to overall hippocampal and cognitive dysfunction in the illness.

Year2016
JournalSchizophrenia
Journal citation2 (16022), pp. 1 - 8
PublisherNature Publishing Group
ISSN2334-265X
Digital Object Identifier (DOI)https://doi.org/10.1038/npjschz.2016.22
Open accessOpen access
Page range1 - 8
Research GroupSchool of Behavioural and Health Sciences
Publisher's version
Place of publicationUnited Kingdom
EditorsJ. Meador-Woodruff
Permalink -

https://acuresearchbank.acu.edu.au/item/85v71/molecular-evidence-of-synaptic-pathology-in-the-ca1-region-in-schizophrenia

  • 75
    total views
  • 103
    total downloads
  • 2
    views this month
  • 1
    downloads this month
These values are for the period from 19th October 2020, when this repository was created.

Export as

Related outputs

Shifting towards a model of mGluR5 dysregulation in schizophrenia: Consequences for future schizophrenia treatment
Matosin, Natalie, Fernandez-Enright, Francesca, Lum, Jeremy S. and Newell, Kelly A.. (2017). Shifting towards a model of mGluR5 dysregulation in schizophrenia: Consequences for future schizophrenia treatment. Neuropharmacology. 115, pp. 73 - 91. https://doi.org/10.1016/j.neuropharm.2015.08.003
NMDA receptor antagonism by phencyclidine reduces NWASP and WAVE1 protein expression and reduces levels of myelination markers in the prefrontal cortex of rats
Andrews, Jessica L., Newell, Kelly A., Matosin, Natalie, Huang, Xu-Feng and Fernandez-Enright, Francesca Elizabeth. (2015). NMDA receptor antagonism by phencyclidine reduces NWASP and WAVE1 protein expression and reduces levels of myelination markers in the prefrontal cortex of rats. Journal of Pharmaceutics and Pharmacology. 3(1), pp. 1 - 8.
Alterations of mGluR5 and its endogenous regulators Norbin, Tamalin and Preso1 in schizophrenia: Towards a model of mGluR5 dysregulation
Matosin, Natalie, Fernandez-Enright, Francesca Elizabeth, Fung, Samantha Jane, Lum, Jeremy Stephen, Engel, Martin, Andrews, Jessica Lee, Huang, Xu-Feng, Weickert, Cynthia Shannon and Newell, Kelly Anne. (2015). Alterations of mGluR5 and its endogenous regulators Norbin, Tamalin and Preso1 in schizophrenia: Towards a model of mGluR5 dysregulation. Acta Neuropathologica. 130(1), pp. 119 - 129. https://doi.org/10.1007/s00401-015-1411-6
Alterations of p75 neurotrophin receptor and Myelin transcription factor 1 in the hippocampus of perinatal phencyclidine treated rats
Andrews, Jessica L., Newell, Kelly A., Matosin, Natalie, Huang, Xu-Feng and Fernandez-Enright, Francesca Elizabeth. (2015). Alterations of p75 neurotrophin receptor and Myelin transcription factor 1 in the hippocampus of perinatal phencyclidine treated rats. Progress in Neuropsychopharmacology and Biological Psychiatry. 56(63), pp. 91 - 97. https://doi.org/10.1016/j.pnpbp.2015.06.003
Genetic variants in Nogo receptor signaling pathways may be associated with early life adversity in schizophrenia susceptibility
Andrews, Jessica L. and Fernandez-Enright, Francesca Elizabeth. (2015). Genetic variants in Nogo receptor signaling pathways may be associated with early life adversity in schizophrenia susceptibility. Biochimica et Biophysica Acta Clinical. 3, pp. 36 - 43. https://doi.org/10.1016/j.bbacli.2014.11.008
Metabotropic glutamate receptor 5, and its trafficking molecules Norbin and Tamalin, are increased in the CA1 hippocampal region of subjects with schizophrenia
Matosin, Natalie, Fernandez-Enright, Francesca Elizabeth, Lum, Jeremy S., Andrews, Jessica L., Engel, Martin, Huang, Xu-Feng and Newell, Kelly A.. (2015). Metabotropic glutamate receptor 5, and its trafficking molecules Norbin and Tamalin, are increased in the CA1 hippocampal region of subjects with schizophrenia. Schizophrenia Research. 166(2017-03-01), pp. 212 - 218. https://doi.org/10.1016/j.schres.2015.05.001
Investigation of genetic variants in ubiquitin enzyme genes involved in the modulation of neurodevelopmental processes: A role in schizophrenia susceptibility?
Andrews, Jessica L. and Fernandez-Enright, Francesca. (2014). Investigation of genetic variants in ubiquitin enzyme genes involved in the modulation of neurodevelopmental processes: A role in schizophrenia susceptibility? Genetics Research. 96(e15), pp. 1 - 9. https://doi.org/10.1017/S0016672314000184
Metabotropic glutamate receptor mGluR2/3 and mGluR5 binding in the anterior cingulate cortex in psychotic and nonpsychotic depression, bipolar disorder and schizophrenia: Implications for novel mGluR-based therapeutics
Matosin, Natalie, Fernandez-Enright, Francesca, Frank, Elisabeth, Deng, Chao, Wong, Jenny, Huang, Xu-Feng and Newell, Kelly A.. (2014). Metabotropic glutamate receptor mGluR2/3 and mGluR5 binding in the anterior cingulate cortex in psychotic and nonpsychotic depression, bipolar disorder and schizophrenia: Implications for novel mGluR-based therapeutics. Journal of Psychiatry and Neuroscience. 39(6), pp. 407 - 416. https://doi.org/10.1503/jpn.130242
Novel implications of Lingo-1 and its signaling partners in schizophrenia
Fernandez-Enright, F., Andrews, J. L., Newell, K. A., Pantelis, C. and Huang, X.-F.. (2014). Novel implications of Lingo-1 and its signaling partners in schizophrenia. Translational Psychiatry. 4, pp. 1 - 8. https://doi.org/10.1038/tp.2013.121
In vivo pharmacological evaluations of novel olanzapine analogues in rats: A potential new avenue for the treatment of schizophrenia
Jafari, Somayeh, Huang, Xu-Feng, Andrews, Jessica L. and Fernandez-Enright, Francesca. (2013). In vivo pharmacological evaluations of novel olanzapine analogues in rats: A potential new avenue for the treatment of schizophrenia. PLoS ONE. 8(12), pp. 1 - 10. https://doi.org/10.1371/journal.pone.0080979
Novel olanzapine analogues presenting a reduced H 1 receptor affinity and retained 5HT 2A/D 2 binding affinity ratio
Jafari, Somayeh, Bouillon, Marc E., Huang, Xu-Feng, Pyne, Stephen G. and Fernandez-Enright, Francesca. (2012). Novel olanzapine analogues presenting a reduced H 1 receptor affinity and retained 5HT 2A/D 2 binding affinity ratio. BMC Pharmacology. 12(1), pp. 1 - 8. https://doi.org/10.1186/1471-2210-12-8
Structural contributions of antipsychotic drugs to their therapeutic profiles and metabolic side effects
Jafari, Somayeh, Fernandez-Enright, Francesca and Huang, Xu-Feng. (2012). Structural contributions of antipsychotic drugs to their therapeutic profiles and metabolic side effects. Journal of Neurochemistry. 120(3), pp. 371 - 384. https://doi.org/10.1111/j.1471-4159.2011.07590.x