Transient impairment of hippocampus-dependent learning and memory in relatively low-dose of acute radiation syndrome is associated with inhibition of hippocampal neurogenesis.
Neurogenesis in the adult hippocampus, which occurs constitutively, is vulnerable to ionizing radiation. In the relatively low-dose exposure of acute radiation syndrome (ARS), the change in the adult hippocampal function is poorly understood. This study analyzed the changes in apoptotic cell death and neurogenesis in the DGs of hippocampi from adult ICR mice with single whole-body gamma-irradiation using the TUNEL method and immunohistochemical markers of neurogenesis, Ki-67 and doublecortin (DCX). In addition, the hippocampus-dependent learning and memory tasks after single whole-body gamma-irradiation were examined in order to evaluate the hippocampus-related behavioral dysfunction in the relatively low-dose exposure of ARS. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 6-12 h after acute gamma-irradiation (a single dose of 0.5 to 4 Gy). In contrast, the number of Ki-67- and DCX-positive cells began to decrease significantly 6 h postirradiation, reaching its lowest level 24 h after irradiation. The level of Ki-67 and DCX immunoreactivity decreased in a dose-dependent manner within the range of irradiation applied (0-4 Gy). In passive avoidance and object recognition memory test, the mice trained 1 day after acute irradiation (2 Gy) showed significant memory deficits, compared with the sham controls. In conclusion, the pattern of the hippocampus-dependent memory dysfunction is consistent with the change in neurogenesis after acute irradiation. It is suggested that a relatively low dose of ARS in adult ICR mice is sufficiently detrimental to interrupt the functioning of the hippocampus, including learning and memory, possibly through the inhibition of neurogenesis.
Kim
Joong-Sun
JS
Department of Veterinary Anatomy, College of Veterinary Medicine and Veterinary Medical Research Center, Chonnam National University, Gwangju, South Korea.
Lee
Hae-June
HJ
Kim
Jong Choon
JC
Kang
Seong Soo
SS
Bae
Chun-Sik
CS
Shin
Taekyun
T
Jin
Jae-Kwang
JK
Kim
Sung Ho
SH
Wang
Hongbing
H
Moon
Changjong
C
D054508:Acute Radiation Syndrome / Q000503:physiopathology*; D000818:Animals; D004307:Dose-Response Relationship, Radiation; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000503:physiopathology* / Q000528:radiation effects*; D007858:Learning / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009416:Nerve Regeneration / Q000528:radiation effects*; D009433:Neural Inhibition / Q000528:radiation effects*; D011829:Radiation Dosage