Aging-dependent changes in the radiation response of the adult rat brain.
OBJECTIVE
To assess the impact of aging on the radiation response in the adult rat brain.


METHODS
Male rats 8, 18, or 28 months of age received a single 10-Gy dose of whole-brain irradiation (WBI). The hippocampal dentate gyrus was analyzed 1 and 10 weeks later for sensitive neurobiologic markers associated with radiation-induced damage: changes in density of proliferating cells, immature neurons, total microglia, and activated microglia.


RESULTS
A significant decrease in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. The WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased after WBI in young rats, but not in old rats. Total microglial numbers decreased after WBI at all ages, but microglial activation increased markedly, particularly in older animals.


CONCLUSIONS
Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in number of immature neurons after WBI, but have a greater inflammatory response. The latter may have an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals.
Schindler
Matthew K
MK
Program in Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. mkschind@wfubmc.edu
Forbes
M Elizabeth
ME
Robbins
Mike E
ME
Riddle
David R
DR
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000473:pathology / Q000502:physiology / Q000528:radiation effects*; D002452:Cell Count; D049109:Cell Proliferation / Q000528:radiation effects; D016371:Cranial Irradiation / Q000379:methods; D018891:Dentate Gyrus / Q000737:chemistry / Q000473:pathology / Q000528:radiation effects; D008297:Male; D017628:Microglia / Q000166:cytology / Q000528:radiation effects*; D009474:Neurons / Q000166:cytology / Q000528:radiation effects*; D051381:Rats; D011916:Rats, Inbred F344