Screening of lipids for long-term brain irradiation effect based on non-targeted lipidomics

Abstract

Irradiation and weightlessness are the main causes of neurological damage in astronauts on long-duration manned flights. Ionizing radiation induces the proliferation of microglia and astrocytes and the production of pro-inflammatory and chemokines, leading to neuroinflammatory responses. Peripheral blood sampling is convenient and serum lipidomic analysis allows the characterisation of the lipid profile of biological fluids in serum after whole brain irradiation (WBI) and the assessment of the long-term effects of radiation-induced brain damage. Therefore, a systematic study of neurological damage after whole brain irradiation using a lipidomic approach can help to elucidate the dose- and time-dependent nature of radiation damage and the associated molecular mechanisms of damage, and provide a corresponding theoretical basis for the selection of targets for space radiation bio-protection. In this study the dose dependence of WBI injury was evaluated by monitoring different factors as, hair removal, body weight, and organ index. Data collected after one month after the WBI upon 10 Gy, 10 Gy × 3, and 30 Gy. Non-targeted lipidomics was used to analyze the differential lipids in serum, one-month after the WBIinduced by different radiation doses. The results indicated that the degree of injury in the 10 Gy × 3 group was between 10 Gy, and 30 Gy groups. The proliferation of microglia (Iba-1+), and astrocytes (GFAP+) in different brain regions (prefrontal cortex, striatum, hippocampus, midbrain, and cerebellum) was also analyzed. When parameters are used in combination that prominently effect long-term inflammatory damage to the hippocampus. Our study showed significant difference in the expression of triacylglycerol, phosphatidylcholine and phosphatidylethanolamine lipids in the serum of rats one month after WBI. A total of 191 differential lipids were found common in the 10 Gy, 10 Gy × 3, and 30 Gy groups relative to the non-irradiated group. The lipids belonging to the subclasses, sphingomyelin, monoacylglycerol, lysophosphatidylethanolamine, ceramide nonhydroxyfatty acidsphingosines, and anacardic acid (Acar) were down-regulated. Lipids that belonged to sulfoquinovosyl diacylglycerol, phosphatidylglycerol, monogalaktos diacylglycerol, lysodiacylglyceryltrimethyl homoserines, and cholesterol ester were up-regulated according to our study. Among these lipids, ω-6 20:4 fatty acids, lysophosphatidylcholines (LPCs), and triglycerides (TAGs) showed a promoting effect on inflammation; however, others such as ceramide (Cer), sphingomyelin (SM) showed an inhibitory effect on inflammation. Overall, our study shows a comprehensive long-term inflammatory response after WBI.