Direct and indirect effects of fetal irradiation on cortical gray and white matter volume in the macaque

Abstract

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.

Figure 1

In the top graph, frontal lobe gray matter (GM) and white matter (WM) volumes for each animal are plotted. Mean volumes for nonirradiated control animals (CON), early gestationally irradiated monkeys (eFIM), and midgestationally irradiated monkeys (mFIM) are indicated by bars. Lower graphs shows individual volumes of nonfrontal lobe GM and WM.