The mechanisms beneath the initiation of neuroinflammation are still inconclusive. Growing evidence proposes the maternal effect on the development of neuroinflammation. In this study, we evaluated the upstream regulators and the indices of neuroinflammation in the hippocampi of female offspring at 3 months old. The accumulation of nuclear factor-κB (NF-κB, 65 kDa), a cytokine-encoding transcription factor, was increased in microglia. The enhanced microglial activation was detected in CA1, CA3 and dentate gyrus (DG) HFD group with upregulation of CD11b and ionized calcium binding adaptor molecule 1 (Iba-1). Moreover, proinflammatory cytokines (including TNFα, IL-1β and IL-6) were significantly increased in HFD group. Peroxisome proliferator-activated receptors γ (PPARγ) is a transcription factor involved in the suppression of NF-κB expression and in encoding endogenous antioxidants (such as catalase and glutathione peroxidases). On the contrary, the expression of nuclear PPARγ was suppressed in hippocampal neurons of the HFD group. In addition, the expressions of glutathione peroxidase 1 (GPx1) was suppressed in HFD group. Oral application with pioglitazone, a PPARγ agonist, effectively ceased the neuroinflammation and reversed the expression of antioxidants in HFD group. Together, these results for the first time demonstrated that maternal HFD triggered the waxing and waning of NF-κB and PPARγ may initiate neuroinflammation in the hippocampus of adult female offspring. Our findings further suggest that PPARγ could be the feasible targets to reprogram the hippocampal impairment induced by maternal HFD.

神经炎症引发的机制仍无定论。越来越多的证据表明母体对神经炎症的发展有影响。在本研究中，我们评估了 3 个月大的雌性后代海马的上游调节因子和神经炎症指标。小胶质细胞中核因子-κB（NF-κB，65 kDa）（一种细胞因子编码转录因子）的积累增加。在 CA1、CA3 和齿状回 (DG) HFD 组中检测到小胶质细胞活化增强，CD11b 和离子钙结合接头分子 1 (Iba-1) 上调。此外，HFD 组促炎细胞因子（包括 TNFα、IL-1β 和 IL-6）显着增加。过氧化物酶体增殖物激活受体 γ (PPARγ) 是一种转录因子，参与抑制 NF-κB 表达和编码内源抗氧化剂（例如过氧化氢酶和谷胱甘肽过氧化物酶）。相反，HFD组海马神经元核PPARγ的表达受到抑制。此外，HFD组谷胱甘肽过氧化物酶1（GPx1）的表达受到抑制。口服PPARγ激动剂吡格列酮可有效终止HFD组的神经炎症并逆转抗氧化剂的表达。总之，这些结果首次证明，母体 HFD 引发 NF-κB 和 PPARγ 的消长可能引发成年女性后代海马的神经炎症。我们的研究结果进一步表明，PPARγ 可能是重新编程母亲 HFD 引起的海马损伤的可行靶点。