Abnormalities of thalamic volume and shape detected in fetally irradiated rhesus monkeys with high dimensional brain mapping

Biol Psychiatry. 2002 May 15;51(10):827-37. doi: 10.1016/s0006-3223(01)01341-5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Macaca mulatta
  • Magnetic Resonance Imaging
  • Pregnancy
  • Radiation Dosage
  • Radiation Injuries* / complications
  • Schizophrenia / etiology
  • Thalamus / abnormalities*
  • Thalamus / embryology*