NeuN+ neuronal nuclei in non-human primate prefrontal cortex and subcortical white matter after clozapine exposure

Tobias B. Halene, Alexey Kozlenkov, Yan Jiang, Amanda C. Mitchell, Behnam Javidfar, Aslihan Dincer, Royce Park, Jennifer Wiseman, Paula L. Croxson, Eustathia Lela Giannaris, Patrick R. Hof, Panos Roussos, Stella Dracheva, Scott E. Hemby, Schahram Akbarian

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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 6 months 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.

Original languageEnglish
Pages (from-to)235-244
Number of pages10
JournalSchizophrenia Research
Volume170
Issue number2-3
DOIs
StatePublished - 1 Feb 2016

Keywords

  • Antipsychotic
  • Clozapine
  • Flow cytometry
  • Monkey
  • Schizophrenia
  • White matter

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