NeuN(+) neuronal nuclei in non-human primate prefrontal cortex and subcortical white matter after clozapine exposure
Department of Radiology, Division of Translational Anatomy
Mental Disorders | Nervous System | Neuroscience and Neurobiology
Increased neuronal densities in subcortical white matter have been reported for some cases with schizophrenia. The underlying cellular and molecular mechanisms remain unresolved. We exposed 26 young adult macaque monkeys for 6months to either clozapine, haloperidol or placebo and measured by structural MRI frontal gray and white matter volumes before and after treatment, followed by observer-independent, flow-cytometry-based quantification of neuronal and non-neuronal nuclei and molecular fingerprinting of cell-type specific transcripts. After clozapine exposure, the proportion of nuclei expressing the neuronal marker NeuN increased by approximately 50% in subcortical white matter, in conjunction with a more subtle and non-significant increase in overlying gray matter. Numbers and proportions of nuclei expressing the oligodendrocyte lineage marker, OLIG2, and cell-type specific RNA expression patterns, were maintained after antipsychotic drug exposure. Frontal lobe gray and white matter volumes remained indistinguishable between antipsychotic-drug-exposed and control groups. Chronic clozapine exposure increases the proportion of NeuN(+) nuclei in frontal subcortical white matter, without alterations in frontal lobe volumes or cell type-specific gene expression. Further exploration of neurochemical plasticity in non-human primate brain exposed to antipsychotic drugs is warranted.
Antipsychotic, Clozapine, Flow cytometry, Monkey, Schizophrenia, White matter
DOI of Published Version
Schizophr Res. 2016 Feb;170(2-3):235-44. doi: 10.1016/j.schres.2015.12.016. Epub 2016 Jan 6. Link to article on publisher's website
Halene TB, Kozlenkov A, Jiang Y, Mitchell AC, Javidfar B, Dincer A, Park R, Wiseman J, Croxson PL, Giannaris EL, Hof PR, Roussos P, Dracheva S, Hemby SE, Akbarian S. (2016). NeuN(+) neuronal nuclei in non-human primate prefrontal cortex and subcortical white matter after clozapine exposure. Radiology Publications. https://doi.org/10.1016/j.schres.2015.12.016. Retrieved from https://escholarship.umassmed.edu/radiology_pubs/160