J Vet Sci.  2012 Mar;13(1):1-6. 10.4142/jvs.2012.13.1.1.

Fast neutron irradiation deteriorates hippocampus-related memory ability in adult mice

• Yang M
• Kim H
• Kim J
• Kim SH
• Kim JC
• Bae CS
• Kim JS
• Shin T
• Moon C

• KMID: 1364996
• DOI: http://doi.org/10.4142/jvs.2012.13.1.1

Abstract

Object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice exposed to cranial fast neutron irradiation (0.8 Gy) were examined to evaluate hippocampus-related behavioral dysfunction following acute exposure to relatively low doses of fast neutrons. In addition, hippocampal neurogenesis changes in adult murine brain after cranial irradiation were analyzed using the neurogenesis immunohistochemical markers Ki-67 and doublecortin (DCX). In the object recognition memory test and contextual fear conditioning, mice trained 1 and 7 days after irradiation displayed significant memory deficits compared to the sham-irradiated controls. The number of Ki-67- and DCX-positive cells decreased significantly 24 h post-irradiation. These results indicate that acute exposure of the adult mouse brain to a relatively low dose of fast neutrons interrupts hippocampal functions, including learning and memory, possibly by inhibiting neurogenesis.

Keyword

fast neutron; hippocampus; learning and memory; neurogenesis

MeSH Terms

Animals
Cranial Irradiation
*Fast Neutrons
Hippocampus/metabolism/physiology/*radiation effects
Immunohistochemistry
Ki-67 Antigen/metabolism
Male
Memory/physiology/*radiation effects
Mice
Mice, Inbred C57BL
Microtubule-Associated Proteins/metabolism
Neurogenesis/physiology/*radiation effects
Neuropeptides/metabolism

Figure

• 

  Fig. 1 Acute fast neutron irradiation transiently decreases object recognition memory in mice. The sham-irradiated controls (1 day after sham-irradiation) and mice 1, 7, and 14 days after acute irradiation with 0.8 Gy of fast neutrons were examined (n = seven for each group). During training, two objects were presented to each mouse for 10 min. After 24 h, one of the previously presented objects was replaced with a novel object (testing). If the mouse remembered the re-presented object, we hypothesized that it would spend more time with the novel object during testing as indicated by a higher percentage of object preference. (A) The sham-irradiated controls and mice 1, 7, and 14 days after irradiation showed equal preference for the two objects during training. (B) During testing, sham-irradiated control and mice trained 14 days after irradiation exhibited a significant preference for the novel object. A significant difference in novel object preference was found between sham-irradiated controls and mice trained 1 and 7 days post-irradiation (p.i). Data are reported as the mean ± SE. *p < 0.05 and **p < 0.01 vs. the sham-irradiated controls.

• 

  Fig. 2 Irradiated mice display a transient deficit in contextual fear conditioning. Sham-irradiated controls (1 day after sham-irradiation) and mice examined 1, 7, and 14 days after acute irradiation with 0.8 Gy of fast neutrons underwent contextual fear conditioning (n = seven for each group). The freezing behavior of the mice was evaluated 24 h after training. Mice trained 1 and 7 days p.i. exhibited lower levels of learning and memory formation than the sham-irradiated controls as indicated by significantly lower rates of freezing during testing. Data are reported as the mean ± SE. **p < 0.01 and ***p < 0.001 vs. sham-irradiated controls.

• 

  Fig. 3 Representative images showing Ki-67-positive proliferating cells and DCX-positive immature progenitor cells in the adult hippocampus dentate gyrus (DG) after fast neutron irradiation. Ki-67 (panels A and B) and DCX immunoreactivity (panels C and D) in the subgranular zone of the DG decreased after exposure to 0.8 Gy of fast neutrons. GCL: granular cell layer. Scale bars = 40 µm.

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