摘要 : Objective This study aimed to characterize the molecular immune networks and microglia reactivity in the nucleus accumbens (NAc) shell affected by fetal nutritional programming leading to addiction-like behavior in the offspring o... 展开 Objective This study aimed to characterize the molecular immune networks and microglia reactivity in the nucleus accumbens (NAc) shell affected by fetal nutritional programming leading to addiction-like behavior in the offspring of Wistar rats. Fetal nutritional programming by energy-dense foods leads to addictionlike behavior in the offspring. Exposure to energy-dense foods also activates systemic and central inflammation in the offspring. Methods Females Wistar rats were exposed to cafeteria (CAF) diet or control diet for 9 weeks (prepregnancy, pregnancy and lactation), and male offspring at 2 months of age were diagnosed with food addiction-like behavior using operant conditioning. Global microarray analysis, RTqPCR, proinflammatory plasma profile and microglia immunostaining were performed in the NAc shell of male rats. SIM-A9 microglia cells were stimulated with IFN-a and palmitic acid, and microglia activation and phagocytosis were determined by RTqPCR and incubation of green-fluorescent latex beads, respectively. Results Microarray analysis in the NAc shell of the male offspring exposed to CAF during development and diagnosed with addiction-like behavior showed increasing in the type I interferon-inducible gene, Ift1, gene network. Genomic and cellular characterization also confirmed microglia hyperreactivity and upregulation of the Ifitl in the NAc shell of animals with addiction-like behavior. In-vitro models demonstrated that microglia do respond to I FN-a promoting a time-dependent genomic expression of Ift1, IL-1 ft and IL-6 followed by increased phagocytosis. Conclusion Prenatal exposure to energy-dense foods primes the IFN type I signaling and microglia complexity in the NAc shell of rats diagnosed with food addiction-like behavior. 收起