Title
NeuN(+) neuronal nuclei in non-human primate prefrontal cortex and subcortical white matter after clozapine exposure
UMMS Affiliation
Department of Radiology, Division of Translational Anatomy
Publication Date
2016-02-01
Document Type
Article
Disciplines
Mental Disorders | Nervous System | Neuroscience and Neurobiology
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 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.
Keywords
Antipsychotic, Clozapine, Flow cytometry, Monkey, Schizophrenia, White matter
DOI of Published Version
10.1016/j.schres.2015.12.016
Source
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
Journal/Book/Conference Title
Schizophrenia research
Related Resources
PubMed ID
26776227
Repository Citation
Halene, Tobias B.; Kozlenkov, Alexey; Jiang, Yan; Mitchell, Amanda C.; Javidfar, Behnam; Dincer, Aslihan; Park, Royce; Wiseman, Jennifer; Croxson, Paula L.; Giannaris, Eustathia Lela; Hof, Patrick R.; Roussos, Panos; Dracheva, Stella; Hemby, Scott E.; and Akbarian, Schahram, "NeuN(+) neuronal nuclei in non-human primate prefrontal cortex and subcortical white matter after clozapine exposure" (2016). Radiology Publications and Presentations. 160.
https://escholarship.umassmed.edu/radiology_pubs/160
Comments
UMass Medical School's Division of Translational Anatomy moved from the Department of Cell and Developmental Biology to the Department of Radiology in March 2015.