Increased interstitial white matter neuron density in the dorsolateral prefrontal cortex of people with schizophrenia.
BACKGROUND
Interstitial white matter neurons (IWMNs) may reflect immature neurons that migrate tangentially to the neocortex from the ganglionic eminence to form cortical interneurons. Alterations of interneuron markers have been detected in gray matter of dorsolateral prefrontal cortex in schizophrenia, and IWMNs are also reported to be altered in schizophrenia. In this study, we considered whether a potential link exists between these two pathological findings.


METHODS
From a cohort of 29 schizophrenia subjects and 37 control subjects, IWMN densities were determined in the dorsolateral prefrontal cortex by counting neuronal nuclear antigen (NeuN) and somatostatin (SST)-positive cells. Double-label immunofluorescence was carried out to determine the overlap between SST+/NeuN+ and SST+/neuropeptide Y + neurons.


RESULTS
We found that density of NeuN + IWMNs in superficial white matter is significantly increased in schizophrenia subjects compared with control subjects. There was a significant negative correlation between SST mRNA expression in gray matter and NeuN + IWMN density. In schizophrenic patients with increased NeuN IWMN density, the density of SST-expressing neurons in white matter was also higher compared with control subjects. A subpopulation of SST immunopositive cells also show coexpression of neuropeptide Y.


CONCLUSIONS
Our study confirmed previous results indicating that the density of NeuN + IWMNs is increased in superficial white matter in schizophrenia. We provide the first evidence that increased IWMN density correlates with a gray matter interneuron deficit, suggesting that migration of interneurons from white matter to the cortex may be deficient in some patients with schizophrenia, consistent with an interneuron deficit in schizophrenia.
Yang
Yang
Y
Schizophrenia Research Institute, University of New South Wales, Sydney, Australia.
Fung
Samantha J
SJ
Rothwell
Alice
A
Tianmei
Si
S
Weickert
Cynthia Shannon
CS
D034961:Antigens, Nuclear / Q000378:metabolism; D054022:Cerebrum / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000473:pathology*; D007395:Interneurons / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology*; D012559:Schizophrenia / Q000378:metabolism / Q000473:pathology*; D013004:Somatostatin / Q000378:metabolism
D034961:Antigens, Nuclear; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; C506808:neuronal nuclear antigen NeuN, human; D013004:Somatostatin