| Objective Radiation therapy is an important treatment modality for primary andmetastatic head and neck tumors. Although white matter necrosis is uncommon withmodern radiation therapy techniques, functional deficits have become increasinglyimportant, having profound effects on quality of life. There are no proven successfullong-term treatments or effective preventative strategies for radiation-induced cognitiveimpairment. Previous studies have indicated that exercise can improve cognitive function,and in which BDNF may play a very important role. In the present study, we investigatedwhether the running exercise after irradiation had the protective effects of theradiation-induced cognitive impairment and the changes in protein expression of BDNFsignaling pathway in the hippocampus were also detected.Methods64healthy Sprague–Dawley rats (male, two month old) were divided into4groups: the control group, the low-intensity exercise group, the moderate-intensity exercisegroup, the high-intensity exercise group (n=16in each group). Animals in the exercisegroup were run on the motor-driven running wheel twice a day (30min in the morning and30min in the afternoon),5days a week for a consecutive3-week period. Behavioral testswere performed after exercise in the order of open field and Morris water maze. These testswere used to evaluate the anxiety level, hippocampal dependent spatial learning andmemory.64Sprague–Dawley rats (male, one month old) received a single dose of20Gyor sham whole-brain irradiation (WBI), behavioral tests were evaluated using open fieldtest and Morris water maze at2months after irradiation. Half of the rats accepted a3-week forced running exercise before the behavior detection. Immunofluorescence was used toevaluate the changes in hippocampal neurogenesis and Western blotting was used to assesschanges in the levels of mature BDNF, phosphorylated TrkB receptor, Akt, ERK, CaMKII,CREB.Results There was no significant difference in open field test among control and threeexercise groups. In the place navigation test, all of the three intensity exercise groupsdecreased latency time compared with the control group but only the moderate-intensityone reached significant (P=0.001). In the spatial probe test, no significant groupdifference was found. Neither WBI nor exercise has an effect on performance in open fieldtest. In the place navigation test, WBI significantly increased latency time compared withthe sham group (P=0.014). Exercise significantly decreased latency time both in shamgroup and irradiation group (P=0.004; P <0.001). In the spatial probe test, no significantgroup difference was found. WBI reduced the number of DCX+(P <0.001) andBrdU+/NeuN+(P <0.001) in the DG, exercise brought159%,211%increase of DCX+cells(P=0.001; P <0.001) and189%,226%increase of BrdU+/NeuN+cells(P <0.001; P <0.001) compared with sham group and irradiated group animals, respectively. WBI reducedexpression of BDNF and phosphorylation of TrkB, Akt, ERK, CaMKII, CREB to62%(P=0.001),46%(P <0.001),66%(P=0.001),85%(P=0.036),70%(P=0.001),71%(P=0.012)compared with sham group. Exercise improve these proteins to175%(P <0.001),128%(P=0.005),164%(P <0.001),179%(P <0.001),196%(P <0.001),130%(P=0.02) comparedwith sham group and90%(P=0.016,80%(P <0.001),91%(P <0.001),136%(P <0.001),126%(P=0.001),98%(P=0.024) compared with irradiation group.Conclusion Our study demonstrates that moderate-intensity forced running exercisesignificantly improved learning and memory in intact animals，BDNF signaling pathwayactivated by exercise is beneficial not only in increasing the number of hippocampalnewborn neurons but also in reducing cognitive functional impairments in irradiated rats. |
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