Sensitivity to radiation-induced apoptosis and neuron loss declines rapidly in the postnatal mouse neocortex

Therapeutic brain irradiation can cause progressive decline in cognitive function, particularly in children, but the reason for this effect is unclear. The study explored whether age-related differences in apoptotic sensitivity might contribute to the increased vulnerability of the young brain to ra...

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Bibliographic Details
Published in:International journal of radiation biology 2005-07, Vol.81 (7), p.545-554
Main Authors: Nakaya, K., Hasegawa, T., Flickinger, J. C., Kondziolka, D. S., Fellows-Mayle, W., Gobbel, G. T.
Format: Article
Language:English
Subjects:
age
Animals
Animals, Newborn - growth & development
Apoptosis
Apoptosis - radiation effects
brain
Child
Child Development
Female
Humans
Immunohistochemistry
infant
Male
Mice
Mice, Inbred C57BL
neocortex
Neocortex - cytology
Neocortex - growth & development
Neocortex - radiation effects
neonate
Neurons - radiation effects
radiation
Radiation Injuries - physiopathology
Risk Factors
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Summary:Therapeutic brain irradiation can cause progressive decline in cognitive function, particularly in children, but the reason for this effect is unclear. The study explored whether age-related differences in apoptotic sensitivity might contribute to the increased vulnerability of the young brain to radiation. Postnatal day 1 (P1) to P30 mice were treated with 0 - 16 Gy whole-body X-irradiation. Apoptotic cells were identified and quantified up to 48 h later using the TdT-UTP nick end-labelling method (TUNEL) and immunohistochemistry for activated caspase-3. The number of neuron-specific nuclear protein (NeuN)-positive and -negative cells were also counted to measure neuronal and non-neuronal cell loss. Significantly greater TUNEL labelling occurred in the cortex of irradiated P1 animals relative to the other age groups, but there was no difference among the P7, P14 and P30 groups. Irradiation decreased the %NeuN-positive cells in the mice irradiated on P1, whereas in P14 animals, irradiation led to an increase in the %NeuN-positive cells. These data demonstrate that neocortical neurons of very young mice are more susceptible to radiation-induced apoptosis. However, this sensitivity decreases rapidly after birth. By P14, acute cell loss due to radiation occurs primarily in non-neuronal populations.
ISSN:0955-3002
1362-3095
DOI:10.1080/09553000500280492