Abnormalities of thalamic volume and shape detected in fetally irradiated rhesus monkeys with high dimensional brain mapping.
BACKGROUND
Prior research has indicated neuroanatomical abnormalities of the thalamus in schizophrenia. To study the possible pathogenesis, an animal model of neurodevelopmental thalamic damage has been developed by applying low-dose radiation to rhesus monkeys in early gestation. Irradiated monkeys sacrificed as infants demonstrate neuronal losses in specific thalamic nuclei and decreases in cortical neuropil.


METHODS
Magnetic resonance scans were collected in adult Rhesus monkeys exposed to irradiation during thalamic neurogenesis (E33-42), after thalamic neurogenesis (E70-81), and in nonirradiated control animals. High dimensional brain mapping was used to compare thalamic volumes and shape characteristics in the three groups of animals.


RESULTS
Animals exposed to irradiation at E33-42 showed a significant bilateral loss of thalamic volumes (> 20%) compared with controls and with animals irradiated at E70-81 when total brain volume was used as a covariate in the analysis. Thalamic volume loss was associated with a nonuniform deformation of thalamic shape.


CONCLUSIONS
A first-trimester, neurodevelopmental insult in the nonhuman primate during thalamic neurogenesis produces a complex pattern of thalamic volume loss and shape deformation in adulthood. Low-dose irradiation of the fetal primate may be useful for modeling key features of the pathology described in schizophrenic patients.
Schindler
Matthew K
MK
Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Wang
Lei
L
Selemon
Lynn D
LD
Goldman-Rakic
Patricia S
PS
Rakic
Pasko
P
Csernansky
John G
JG
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D011247:Pregnancy; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000150:complications; D012559:Schizophrenia / Q000209:etiology; D013788:Thalamus / Q000002:abnormalities* / Q000196:embryology*