Metabotropic glutamate receptor 5, and its trafficking molecules Norbin and Tamalin, are increased in the CA1 hippocampal region of subjects with schizophrenia

Journal article


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
AuthorsMatosin, Natalie, Fernandez-Enright, Francesca Elizabeth, Lum, Jeremy S., Andrews, Jessica L., Engel, Martin, Huang, Xu-Feng and Newell, Kelly A.
Abstract

Metabotropic glutamate receptor 5 (mGluR5) is involved in hippocampal-dependent learning and memory, which are processes disrupted in schizophrenia. Recent evidence from human genetic and animal studies suggests that the regulation of mGluR5, including its interaction with trafficking molecules, may be altered in the disorder. However there have been no investigations of hippocampal mGluR5 or mGluR5 trafficking molecules in the postmortem schizophrenia brain to confirm this. In the present study, we investigated whether protein expression of mGluR5, as well as Norbin and Tamalin (modulators of mGluR5 signalling and trafficking), might be altered in the schizophrenia brain, using postmortem samples from the hippocampal CA1 region of schizophrenia subjects and matched controls (n = 20/group). Protein levels of mGluR5 (total: 42%, p < 0.001; monomer: 25%, p = 0.011; dimer: 52%, p < 0.001) and mGluR5 trafficking molecules (Norbin: 47%, p < 0.001; Tamalin: 34%, p = 0.009) were significantly higher in schizophrenia subjects compared to controls. To determine any influence of antipsychotic drug treatment, all proteins were also correlated with lifetime chlorpromazine equivalents in patients, and separately measured in the hippocampus of rats exposed to haloperidol or olanzapine treatment. mGluR5 was negatively correlated with lifetime antipsychotic drug exposure in schizophrenia patients, suggesting antipsychotic drugs could reduce mGluR5 protein in schizophrenia subjects. In contrast, mGluR5 and mGluR5 trafficking molecules were not altered in the hippocampus of antipsychotic drug treated rats. This investigation provides strong support for the hypothesis that mGluR5 is involved in the pathology of schizophrenia, and that alterations to mGluR5 trafficking might contribute to the hippocampal-dependent cognitive dysfunctions associated with this disorder.

KeywordsmGluR5; hippocampus; norbin; tamalin; trafficking; schizophrenia
Year2015
JournalSchizophrenia Research
Journal citation166 (2017-03-01), pp. 212 - 218
PublisherElsevier B.V.
ISSN0920-9964
Digital Object Identifier (DOI)https://doi.org/10.1016/j.schres.2015.05.001
Page range212 - 218
Research GroupSchool of Behavioural and Health Sciences
Publisher's version
File Access Level
Controlled
Place of publicationNetherlands
Permalink -

https://acuresearchbank.acu.edu.au/item/85x34/metabotropic-glutamate-receptor-5-and-its-trafficking-molecules-norbin-and-tamalin-are-increased-in-the-ca1-hippocampal-region-of-subjects-with-schizophrenia

Restricted files

Publisher's version

  • 67
    total views
  • 0
    total downloads
  • 3
    views this month
  • 0
    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
Molecular evidence of synaptic pathology in the CA1 region in schizophrenia
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
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
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