title: Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway.
abstract: Cranial radiotherapy induces progressive and debilitating cognitive deficits, particularly in long-term cancer survivors, which may in part be caused by the reduction of hippocampal neurogenesis. Previous studies suggested that voluntary exercise can reduce the cognitive impairment caused by radiation therapy. However, there is no study on the effect of forced wheel exercise and little is known about the molecular mechanisms mediating the effect of exercise. In the present study, we investigated whether the forced running exercise after irradiation had the protective effects of the radiation-induced cognitive impairment. Sixty-four Male Sprague-Dawley rats received a single dose of 20Gy or sham whole-brain irradiation (WBI), behavioral test was evaluated using open field test and Morris water maze at 2months after irradiation. Half of the rats accepted a 3-week forced running exercise before the behavior detection. Immunofluorescence was used to evaluate the changes in hippocampal neurogenesis and Western blotting was used to assess changes in the levels of mature brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine receptor kinase B (TrkB) receptor, protein kinase B (Akt), extracellular signal-regulated kinase (ERK), calcium-calmodulin dependent kinase (CaMKII), cAMP-calcium response element binding protein (CREB) in the BDNF-pCREB signaling. We found forced running exercise significantly prevented radiation-induced cognitive deficits, ameliorated the impairment of hippocampal neurogenesis and attenuated the down-regulation of these proteins. Moreover, exercise also increased behavioral performance, hippocampal neurogenesis and elevated BDNF-pCREB signaling in non-irradiation group. These results suggest that forced running exercise offers a potentially effective treatment for radiation-induced cognitive deficits.
authors: Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China.
authors: Jian-feng
authors: JF
authors: Ji
authors: Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China.
authors: Sheng-jun
authors: SJ
authors: Ji
authors: Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China.
authors: Rui
authors: R
authors: Sun
authors: Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China.
authors: Kun
authors: K
authors: Li
authors: Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China.
authors: Yuan
authors: Y
authors: Zhang
authors: Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China.
authors: Li-yuan
authors: LY
authors: Zhang
authors: Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China. Electronic address: dryetian@hotmail.com.
authors: Ye
authors: Y
authors: Tian
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology* / Q000528:radiation effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003071:Cognition / Q000528:radiation effects*; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects; D008297:Male; D018782:Maze Learning; D055495:Neurogenesis / Q000528:radiation effects*; D010805:Physical Conditioning, Animal / Q000009:adverse effects*; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000528:radiation effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: BDNF; Cognitive impairments; Exercise; Radiation