Revealing the Increased Stress Response Behavior through Transcriptomic Analysis of Adult Zebrafish Brain after Chronic Low to Moderate Dose Rates of Ionizing Radiation

Simple Summary The increasing use of radiopharmaceuticals for medical diagnostics and radiotherapy raises concerns regarding health risks for both humans and the environment. Additionally, in the context of major nuclear accidents like in Chernobyl and Fukushima, very little is known about the effects of chronic exposure to low and moderate dose rates of ionizing radiation (IR). Many studies demonstrated the sensibility of the developmental brain, but little data exists for IR at low dose rates and their impact on adults. In this study, we characterized the molecular mechanisms that orchestrate stress behavior caused by chronic exposure to low to moderate dose rates of IR using the adult zebrafish model. We observed the establishment of a congruent stress response at both the molecular and individual levels. High levels of ionizing radiation (IR) are known to induce neurogenesis defects with harmful consequences on brain morphogenesis and cognitive functions, but the effects of chronic low to moderate dose rates of IR remain largely unknown. In this study, we aim at defining the main molecular pathways impacted by IR and how these effects can translate to higher organizational levels such as behavior. Adult zebrafish were exposed to gamma radiation for 36 days at 0.05 mGy/h, 0.5 mGy/h and 5 mGy/h. RNA sequencing was performed on the telencephalon and completed by RNA in situ hybridization that confirmed the upregulation of oxytocin and cone rod homeobox in the parvocellular preoptic nucleus. A dose rate-dependent increase in differentially expressed genes (DEG) was observed with 27 DEG at 0.05 mGy/h, 200 DEG at 0.5 mGy/h and 530 DEG at 5 mGy/h. Genes involved in neurotransmission, neurohormones and hypothalamic-pituitary-interrenal axis functions were specifically affected, strongly suggesting their involvement in the stress response behavior observed after exposure to dose rates superior or equal to 0.5 mGy/h. At the individual scale, hypolocomotion, increased freezing and social stress were detected. Together, these data highlight the intricate interaction between neurohormones (and particularly oxytocin), neurotransmission and neurogenesis in response to chronic exposure to IR and the establishment of anxiety-like behavior.