Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat.
The generation of new neurons in the adult mammalian brain has been documented in numerous recent reports. Studies undertaken so far indicate that adult hippocampal neurogenesis is related in a number of ways to hippocampal function.Here, we report that subjecting adult rats to fractionated brain irradiation blocked the formation of new neurons in the dentate gyrus of the hippocampus. At different time points after the termination of the irradiation procedure, the animals were tested in two tests of short-term memory that differ with respect to their dependence on hippocampal function. Eight and 21 days after irradiation, the animals with blocked neurogenesis performed poorer than controls in a hippocampus-dependent place-recognition task, indicating that the presence of newly generated neurons may be necessary for the normal function of this brain area. The animals were never impaired in a hippocampus-independent object-recognition task. These results are in line with other reports documenting the functional significance of newly generated neurons in this region. As our irradiation procedure models prophylactic cranial irradiation used in the treatment of different cancers, we suggest that blocked neurogenesis contributes to the reported deleterious side effects of this treatment, consisting of memory impairment, dysphoria and lethargy.
Madsen
T M
TM
Laboratory of Neuropsychiatry, Department of Psychiatry O-6102, H:S Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
Kristjansen
P E G
PE
Bolwig
T G
TG
Wörtwein
G
G
D000818:Animals; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000502:physiology / Q000528:radiation effects*; D018891:Dentate Gyrus / Q000254:growth & development / Q000503:physiopathology* / Q000528:radiation effects*; D005106:Exploratory Behavior / Q000502:physiology / Q000528:radiation effects; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000502:physiology / Q000528:radiation effects; D008569:Memory Disorders / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000502:physiology / Q000528:radiation effects*; D011878:Radiotherapy / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000502:physiology / Q000528:radiation effects*
D001973:Bromodeoxyuridine