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.

引发神经炎症的机制尚无定论。越来越多的证据表明，母体对神经炎症的发展具有影响。在这项研究中，我们评估了3个月大的雌性后代的上游调节因子和海马神经炎症指数。小胶质细胞中编码细胞因子的转录因子核因子-κB（NF-κB，65 kDa）的积累增加。在CA1，CA3和齿状回（DG）HFD组中检测到增强的小胶质细胞活化，其中CD11b和离子钙结合衔接子分子1（Iba-1）上调。此外，HFD组的促炎细胞因子（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表达并编码内源性抗氧化剂（例如过氧化氢酶和谷胱甘肽过氧化物酶）。相反，在HFD组的海马神经元中核PPARγ的表达被抑制。另外，在HFD组中谷胱甘肽过氧化物酶1（GPx1）的表达被抑制。PPARγ激动剂吡格列酮口服可有效停止神经炎症并逆转HFD组抗氧化剂的表达。在一起，这些结果首次证明母体HFD触发了NF-κB的蜡化和减弱，而PPARγ可能引发成年雌性后代海马的神经炎症。