Direct and indirect effects of fetal irradiation on cortical gray and white matter volume in the macaque.
BACKGROUND
Schizophrenia is associated with reductions in thalamic neuronal number and cortical gray matter volume. Exposure of nonhuman primates to x-irradiation in early gestation has previously been shown to decrease thalamic volume and neuronal number. Here we examine whether early gestational irradiation also results in cortical volume reduction.


METHODS
High-resolution, T1-weighted magnetic resonance scans were collected in adult monkeys 1) exposed to irradiation during the early gestational period (E33-E42) corresponding to thalamic neurogenesis, 2) irradiated in midgestation (E70-81) during neocortical neurogenesis, and 3) not exposed to irradiation. Cortical gray matter and white matter volumes were derived via manual segmentation; frontal and nonfrontal volumes were distinguished via sulcal landmarks.


RESULTS
Monkeys irradiated in early gestation exhibited a trend reduction in nonfrontal gray matter volume (17%) and significant reductions in white matter volume in frontal (26%) and nonfrontal (36%) lobes. Monkeys irradiated in midgestation had smaller gray (frontal: 28%; nonfrontal: 22%) and white matter (frontal: 29%; nonfrontal: 38%) volumes.


CONCLUSIONS
The cortical deficits observed in midgestationally irradiated monkeys are consistent with a reduction in cortical neuronal number. Cortical volume reductions following early gestational irradiation may be secondary to reduced thalamic neuronal number and therefore model the thalamocortical pathology of schizophrenia.
Selemon
Lynn D
LD
Department of Neurobiology, Yale University School of Medicine, PO Box 208001, New Haven, CT 06520-8001, USA. ldselemon@aol.com
Wang
Lei
L
Nebel
Mary Beth
MB
Csernansky
John G
JG
Goldman-Rakic
Patricia S
PS
Rakic
Pasko
P
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology / Q000528:radiation effects*; D005260:Female; D008251:Macaca; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011832:Radiation Injuries / Q000473:pathology*; D013788:Thalamus / Q000473:pathology / Q000528:radiation effects