Department of Biochemistry, College of Medicine, Universidad Autónoma de Nuevo León.
Neurometabolism Unit, Center for Research and Development in Health Sciences, Universidad Autónoma de Nuevo León.
Neuroreport. 2022 Aug 2;33(12):495-503. doi: 10.1097/WNR.0000000000001784. Epub 2022 Jun 28.
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.
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.
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.
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.
本研究旨在描述受胎儿营养编程影响的伏隔核（NAc）壳中的分子免疫网络和小胶质细胞反应，该编程导致 Wistar 大鼠后代出现类似成瘾的行为。高能量食物的胎儿营养编程可导致后代出现类似成瘾的行为。暴露于高能量食物也会激活后代的全身和中枢炎症。
雌性 Wistar 大鼠接受自助餐厅（CAF）饮食或对照饮食 9 周（受孕前、怀孕和哺乳期），并在 2 个月大时通过操作性条件反射诊断出具有食物成瘾样行为的雄性后代。对雄性大鼠 NAc 壳中的基因进行全基因组微阵列分析、RTqPCR、促炎血浆谱和小胶质细胞免疫染色。用 IFN-α和棕榈酸刺激 SIM-A9 小胶质细胞，并通过 RTqPCR 和孵育绿色荧光乳胶珠分别测定小胶质细胞的激活和吞噬作用。
在发育过程中暴露于 CAF 并被诊断出具有类似成瘾行为的雄性后代 NAc 壳中的微阵列分析显示，Ift1 基因的 I 型干扰素诱导基因网络增加。基因组和细胞特征也证实了具有类似成瘾行为的动物 NAc 壳中小胶质细胞的过度活跃和 Ifit1 的上调。体外模型表明，小胶质细胞确实对 IFN-α有反应，促进了 Ift1、IL-1β和 IL-6 的基因表达，随后吞噬作用增加。
产前暴露于高能量食物会使大鼠 NAc 壳中的 I 型干扰素信号和小胶质细胞复杂性发生变化，这些大鼠被诊断出具有食物成瘾样行为。
