Elizabeth Scarr1, Shaun Hopper1, Valentina Vos1, Myoung Suk Seo1, Ian Paul Everall1, Timothy Douglas Aumann1, Gursharan Chana1, Brian Dean1. 1. From the Molecular Psychiatry Laboratory, University of Melbourne, Victoria, Australia (Scarr, Hopper, Vos, Suk Seo, Dean); the Midbrain Dopamine Plasticity Laboratory, the Florey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria, Australia (Aumann); the Centre for Mental Health, Faculty of Health, Arts and Design, Swinburne University, Victoria, Australia (Dean); the Department of Psychiatry, University of Melbourne, Victoria, Australia (Everall); the Integrative Biological Psychiatry Laboratory, Centre for Neural Engineering, University of Melbourne, Victoria, Australia (Chana); and the Melbourne Veterinary School, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Victoria, Australia (Scarr).
Abstract
BACKGROUND: Results of neuroimaging and postmortem studies suggest that people with schizophrenia may have lower levels of muscarinic M1 receptors (CHRM1) in the cortex, but not in the hippocampus or thalamus. Here, we use a novel immunohistochemical approach to better understand the likely cause of these low receptor levels. METHODS: We determined the distribution and number of CHRM1-positive (CHRM1+) neurons in the cortex, medial dorsal nucleus of the thalamus and regions of the hippocampus from controls (n = 12, 12 and 5, respectively) and people with schizophrenia (n = 24, 24 and 13, respectively). RESULTS: Compared with controls, levels of CHRM1+ neurons in people with schizophrenia were lower on pyramidal cells in layer III of Brodmann areas 9 (-44%) and 17 (-45%), and in layer V in Brodmann areas 9 (-45%) and 17 (-62%). We found no significant differences in the number of CHRM1+ neurons in the medial dorsal nucleus of the thalamus or in the hippocampus. LIMITATIONS: Although diagnostic cohort sizes were typical for this type of study, they were relatively small. As well, people with schizophrenia were treated with antipsychotic drugs before death. CONCLUSION: The loss of CHRM1+ pyramidal cells in the cortex of people with schizophrenia may underpin derangements in the cholinergic regulation of GABAergic activity in cortical layer III and in cortical/subcortical communication via pyramidal cells in layer V.
BACKGROUND: Results of neuroimaging and postmortem studies suggest that people with schizophrenia may have lower levels of muscarinic M1 receptors (CHRM1) in the cortex, but not in the hippocampus or thalamus. Here, we use a novel immunohistochemical approach to better understand the likely cause of these low receptor levels. METHODS: We determined the distribution and number of CHRM1-positive (CHRM1+) neurons in the cortex, medial dorsal nucleus of the thalamus and regions of the hippocampus from controls (n = 12, 12 and 5, respectively) and people with schizophrenia (n = 24, 24 and 13, respectively). RESULTS: Compared with controls, levels of CHRM1+ neurons in people with schizophrenia were lower on pyramidal cells in layer III of Brodmann areas 9 (-44%) and 17 (-45%), and in layer V in Brodmann areas 9 (-45%) and 17 (-62%). We found no significant differences in the number of CHRM1+ neurons in the medial dorsal nucleus of the thalamus or in the hippocampus. LIMITATIONS: Although diagnostic cohort sizes were typical for this type of study, they were relatively small. As well, people with schizophrenia were treated with antipsychotic drugs before death. CONCLUSION: The loss of CHRM1+ pyramidal cells in the cortex of people with schizophrenia may underpin derangements in the cholinergic regulation of GABAergic activity in cortical layer III and in cortical/subcortical communication via pyramidal cells in layer V.
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