Progress in Radiation-Induced Cognitive Deficits Revealed by Researchers at IMP
Researchers of the radiation medicine group at Institute of Modern Physics, Chinese Academy of Sciences (IMP) revealed the regulation mechanism involved in the cognitive deficits induced by carbon ions generated by the Heavy Ion Research Facility in Lanzhou (HIRFL).
The impact of cognitive impairment in the primary and metastatic brain tumor patient’s quality of life is recognized as second only to survival in clinical trials. With the development of the combination and precision therapy, patient's overall survival time is prolonged significantly. Thus, the prevention of irradiation-induced cognitive deficits has grown up to become a hot topic of radiation medicine.
The study successfully built the mouse model of cognitive deficits, and a total of 63 proteins in the mitochondria were identified from LC-MS/MS analysis, which linked to the mitochondrial bioenergetic process and oxidative stress. Moreover, we demonstrated the disruptions of mitochondrial homeostasis and redox balance, which consequently led to an energy crisis and persistent oxidative damage in the hippocampus region. Furthermore, co-modulation of NF-E2-related factor 2 (NRF2) and PTEN induced putative kinase 1 (PINK1) may be in charge of initiation and restoration of the cognitive impairments in a mouse model and hippocampal neuronal cells of carbon ion irradiation via modulation of NRF2 and PINK1 expressions.
This is the first study to show the key regulatory mechanism of cognitive dysfunction/repair mediated by carbon ions (Figure 1), and to evaluate the NRF2 and PINK1 as the potential targets for preventing radiation-induced cognitive dysfunction. We provide a new way of thinking about normal tissue protection for improving radiotherapy.
This work was financially supported by the Key Program of National Natural Science Foundation of China, National Key Projects of Research and Development, National Natural Science Foundation of China, and the Western Talent Program of Chinese Academy of Sciences.
The article can be linked as follows: https://doi.org/10.1016/j.redox.2018.04.012