Maternal high-dense diet programs interferon type I signaling and microglia complexity in the nucleus accumbens shell of rats showing food addiction-like behavior

Neuroreport. 2022 Jun 28. doi: 10.1097/WNR.0000000000001784. Online ahead of print.

Abstract

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 addiction-like 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-α 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 Ifit1 in the NAc shell of animals with addiction-like behavior. In-vitro models demonstrated that microglia do respond to IFN-α promoting a time-dependent genomic expression of Ift1, IL-1β 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.