Orignal articlesDirect and indirect effects of fetal irradiation on cortical gray and white matter volume in the macaque
Section snippets
Methods and materials
Thirteen adult macaque monkeys were analyzed in this study (Table 1). Three had been exposed to x-irradiation during the period of thalamogenesis (E33-42) in early gestation (eFIM); three had been irradiated in midgestation (mFIM) when neocortical neurons are generated (E70-E81), and seven were nonirradiated control animals (CON). The irradiation protocol has been described in detail previously (Algan and Rakic 1997). The exact time of exposure and dose of irradiation is shown in Table 1.
Frontal lobe gray matter
Frontal lobe GM volume in eFIMs was reduced by 13% compared with control subjects whereas that of mFIMs was 28% smaller than control animals (Figure 1, Table 2). There was a significant group effect (F2,10 = 5.57; p = .024) for GM (ranks). Post hoc comparison revealed that GM in mFIMs was significantly reduced compared with control animals; the difference in GM volume between eFIM and CON was not significant (Table 2).
Frontal lobe white matter
Frontal lobe WM was reduced by 26% in the eFIMs and by 29% in the mFIMs
Discussion
Monkeys that were exposed to irradiation in midgestation, when cortical neurons are undergoing final mitosis, exhibited pronounced deficits in cortical GM volume undoubtedly reflecting a substantial reduction in cortical neuronal number in these animals. Early gestational irradiation resulted in a more modest decreases in cortical GM volume in the posterior (nonfrontal) lobes and in the frontal lobe where the reduction did not reach significance although the magnitude (13%) of the reduction in
References (98)
- et al.
Decreased density of tyrosine hydroxylase-immunoreactive axons in the entorhinal cortex of schizophrenic subjects
Biol Psychiatry
(2000) - et al.
The thalamus and the schizophrenia phenotypeFailure to replicate reduced volume
Biol Psychiatry
(1999) - et al.
Problems with ratio and proportion measures of imaged cerebral structures
Psychiatry Res
(1991) - et al.
Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring
Schizophr Res
(2003) - et al.
Genesis of the primate neostriatum[3H]thymidine autoradiographic analysis of the time of neuron origin in the rhesus monkey
Neuroscience
(1979) - et al.
Neurogenesis of the nucleus accumbens septi and neighboring septal nuclei in the rhesus monkeyA combined [3H]thymidine and electron microscopic study
Neuroscience
(1980) - et al.
Maternal cytokine levels during pregnancy and adult psychosis
Brain Behav Immun
(2001) - et al.
A postmortem study of the mediodorsal nucleus of the thalamus in schizophrenia
Schizophr Res
(2003) - et al.
Schizophrenia and anteroventral thalamic nucleusselective decrease of parvalbumin-immunoreactive thalamocortical projection neurons
Psychiatry Res
(1998) - et al.
The ventral lateral posterior nucleus of the thalamus in schizophreniaA post-mortem study
Psychiatry Res
(2002)
Volumes of association thalamic nuclei in schizophreniaA postmortem study
Schizophr Res
Schizophrenia as a chronic active brain processA study of progressive brain structural change subsequent to the onset of schizophrenia
Pyschiatr Res
Vitamin D3 and brain development
Neuroscience
Cytokine regulation of embryonic rat dopamine and serotonin neuronal survival in vitro
Int J Develop Neurosci
Meta-analysis of thalamic size in schizophrenia
Biol Psychiatry
Brain structure, genetic liability, and psychotic symptoms in subjects at high risk of developing schizophrenia
Biol Psychiatry
The time of genesis, embryonic origin and differentiation of the brain stem monoamine neurons in the rhesus monkey
Develop Brain Res
Obstetric complications, neurodevelopmental deviance, and risk of schizophrenia
J Psychiatr Res
EEG, cognitive and psychopathological abnormalities in children irradiated in utero
Int J Psychophysiol
Cytokine effects on cortical neuron MAP-2 immunoreactivityimplications for schizophrenia
Biol Psychiatry
Correction for head size in brain-imaging measurements
Psychiatry Res
MRI anatomy of schizophrenia
Biol Psychiatry
Bayesian construction of geometrically based cortical thickness metrics
Neuroimage
Total nerve cell number in neocortex in chronic schizophrenic and controls estimated using optical disectors
Biol Psychiatry
Volumetric evaluation of the thalamus in schizophrenic male patients using magnetic resonance imaging
Biol Psychiatry
Dynamic programming generation of boundaries of local coordinatized submanifolds in the neocortexApplication to the planum temporale
Neuroimage
Validating cortical surface analysis of medial prefrontal cortex
Neuroimage
Abnormalities of thalamic volume and shape detected in fetally-irradiated rhesus monkeys with high dimensional brain mapping
Biol Psychiatry
The reduced neuropil hypothesisA circuit based model of schizophrenia
Biol Psychiatry
Magnetic resonance image tissue classification using a partial volume model
Neuroimage
A review of MRI findings in schizophrenia
Schizopr Res
Total number of neurons in the prefrontal cortex in schizophrenics and controls
J Psychiatr Res
MRI brain abnormalities in chronic schizophreniaOne process or more?
Biol Psychiatry
Reduced number of mediodoral and anterior thalamic neurons in schizophrenia
Biol Psychiatry
Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects
Am J Psychiatry
Radiation-induced, lamina-specific deletions of neurons in the primate visual cortex
J Comp Neurol
Regional brain abnormalities in schizophrenia measured with magnetic resonance imaging
JAMA
Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging
Science
Volumes of brain structures in twins discordant for schizophrenia
Arch Gen Psychiatry
Brain morphology and schizophrenia. A magnetic resonance imaging study of limbic, prefrontal cortex, and caudate structures
Arch Gen Psychiatry
Maternal exposure to respiratory infections and adult schizophrenia spectrum disordersA prospective birth cohort study
Schizophr Bull
PET and MRI of the thalamus in never-medicated patients with schizophrenia
Am J Psychiatry
Magnetic resonance imaging of the thalamic mediodorsal nucleus and pulvinar in schizophrenia and schizotypal personality disorder
Arch Gen Psychiatry
Postmortem assessment of thalamic nuclear volumes in subjects with schizophrenia
Am J Psychiatry
Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia
Proc Natl Acad Sci U S A
Two nonhuman primate models of psychosisFetal irradiation and amphetamine sensitization
Soc Neurosci Abst
Hippocampal morphometry in schizophrenia by high dimensional brain mapping
Proc Natl Acad Sci U S A
Abnormalities of thalamic volume and shape in schizophrenia
Am J Psychiatry
Hippocampal deformities in schizophrenia characterized by high dimensional brain mapping
Am J Psychiatry
Cited by (34)
Nonhuman primate models in the study of spaceflight stressors: Past contributions and future directions
2021, Life Sciences in Space ResearchCitation Excerpt :In the only study cited, rhesus monkeys were exposed to X-ray irradiation during early- and mid-gestation and cortical gray and white matter volumes were recorded. Results from this work showed that early-gestation exposure reduced nonfrontal gray matter volume (17%) and white matter volume in frontal (26%) and nonfrontal (36%) lobes, whereas mid-gestation irradiation resulted in smaller gray (frontal: 28%; nonfrontal: 22%) and white matter (frontal: 29%; nonfrontal: 38%) volumes (Selemon et al., 2005). Such observations suggest that changes in NHP brain structure and function may be highly sensitive to radiation exposure.
Reduced Midbrain Dopamine Neuron Number in the Adult Non-human Primate Brain after Fetal Radiation Exposure
2020, NeuroscienceCitation Excerpt :It is particularly noteworthy that the timing of radiation exposure is a critical determinant of the resulting behavioral deficits, as for instance radiation exposure at embryonic day 11 (E11) in the mouse results in both spatial and reference memory deficits whereas following E10 exposure spatial memory is spared (Verreet et al., 2016). Previous studies of fetal irradiation in the non-human primate have also established that the pathology associated with x-irradiation is dependent on the timing of exposure (Algan and Rakic, 1997; Schindler et al., 2002; Selemon et al., 2005, 2009, 2013). Indeed, the prolonged gestational period of neurogenesis in the non-human primate brain allows for targeting of subcortical versus cortical populations of neurons.
Motor stereotypies and cognitive perseveration in non-human primates exposed to early gestational irradiation
2013, NeuroscienceCitation Excerpt :Our previous studies have uncovered a remarkable degree of similarity between the neuropathology following early gestational exposure to radiation in the macaque and the neuropathology of schizophrenia. Widespread, but non-uniform, volume deficits have been observed most prominently in the thalamus, cortical gray matter and putamen (Schindler et al., 2002; Selemon et al., 2005, 2009; Aldridge et al., 2012). A similar global neuropathologic profile has been described in schizophrenia (Harrison, 1999; Selemon, 2001; Shenton et al., 2001, 2010).
Primate models of schizophrenia: Future possibilities
2009, Progress in Brain ResearchCitation Excerpt :Thus, we should always be cautious about negative results in rodent models, and encourage further research in more elaborate models when warranted. NHP models using irradiation (Selemon et al., 2005) or chronic amphetamine exposure (Selemon et al., 2007) have already provided insights regarding circuit changes, and AAV technology promises to further our understanding of genetic insults on PFC structure and function. As schizophrenia is a disorder of the association cortices, primate models will be important for understanding the impact of genetic insults on the elaborate neuronal architecture and cortical circuitry distinct to the primate brain.