Abstract
BackgroundEarly gestation represents a period of vulnerability to environmental insult that has been associated with adult psychiatric disease. However, little is known about how prenatal perturbation translates into adult brain dysfunction. Here, we use a longitudinal study design to examine the effects of disruption of early gestational neurogenesis on brain volume in the non-human primate.Methods and Principal FindingsFive Rhesus macaques were exposed to x-irradiation in early gestation (E30–E41), and four control monkeys were sham-irradiated at comparable ages. Whole brain magnetic resonance imaging was performed at 6 months, 12 months, and 3 and 5 years of age. Volumes of whole cerebrum, cortical gray matter, caudate, putamen, and thalamus were estimated using semi-automated segmentation methods and high dimensional brain mapping. Volume reductions spanning all ages were observed in irradiated monkeys in the putamen (15–24%, p = 0.01) and in cortical gray matter (6–15%, p = 0.01). Upon covarying for whole cerebral volume, group differences were reduced to trend levels (putamen: p = 0.07; cortical gray matter: p = 0.08). No group-by-age effects were significant.ConclusionsDue to the small number of observations, the conclusions drawn from this study must be viewed as tentative. Early gestational irradiation may result in non-uniform reduction of gray matter, mainly affecting the putamen and cerebral cortex. This may be relevant to understanding how early prenatal environmental insult could lead to brain morphological differences in neurodevelopmental diseases.
Highlights
Gestation has been identified as a vulnerable period for human brain development
Gestational irradiation may result in non-uniform reduction of gray matter, mainly affecting the putamen and cerebral cortex
This may be relevant to understanding how early prenatal environmental insult could lead to brain morphological differences in neurodevelopmental diseases
Summary
Gestation has been identified as a vulnerable period for human brain development. Substance abuse in early gestation is detrimental to normal brain development as heavy maternal alcohol consumption in the first trimester has been linked to anxiety and depression disorders in offspring [3]. A wide range of prenatal environmental stressors, e.g., maternal infection, maternal malnutrition, Rh incompatibility, have been shown to increase the incidence of adult schizophrenia, and the first two trimesters of human fetal development have been identified as periods of particular susceptibility [6,7,8,9,10,11,12,13]. Gestation represents a period of vulnerability to environmental insult that has been associated with adult psychiatric disease. We use a longitudinal study design to examine the effects of disruption of early gestational neurogenesis on brain volume in the non-human primate
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