Objective  To investigate the protective effects of secoisolarciresinol digucoside (SDG) on trans fatty acid (TFA)-induced brain inflammatory response and oxidative stress in offspring mice, and to explore the roles of brain-derived neurotrophic factor (BDNF) 28 and tropomyosin receptor kinase B (TrkB) in this process.

Methods  Female C57BL/6 mice were used in the study. First, pregnant C57BL/6 mice were divided into 5 groups, receiving a normal diet, TFA, low-dose SDG, medium-dose SDG, and high-dose SDG, respectively. After birth, the offspring of the normal diet and TFA groups were subdivided into 2 groups, the normal diet during pregnancy group and the TFA during pregnancy group. The offspring of the low, medium, and high-dose SDG during pregnancy groups were subdivided into 3 groups of low, medium, and high-dose SDG. As a result, the offspring were divided into 13 groups during the lactation period. Only the mother mice were exposed to TFA or SDG intervention. The growth status of the offspring was monitored. After 21 days of lactation, the offspring were sacrificed and the relevant indicators, including pathological changes in the hippocampal region of the brain, levels of tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ), antioxidant levels, and BDNF and TrkB mRNA and protein expression levels, were measured.

Result Maternal TFA exposure and SDG intervention did not result in significant differences in the weight, brain weight, and brain weight coefficient of offspring (P > 0.05). TFA exposure during pregnancy and TFA exposure during pregnancy + lactation led to pathological changes in offspring brain tissue, which were ameliorated by SDG intervention. TFA exposure increased the levels of inflammatory factors (IFN-γ and TNF-α) and oxidative stress markers (increased malondialdehyde MDA levels and decreased superoxide dismutase SOD activity and glutathione/total glutathione ratio GSH/t-GSH, P < 0.05) in offspring brains. In addition, TFA exposure upregulated the expression of BDNF mRNA (during pregnancy and pregnancy + lactation) and BDNF protein (during pregnancy, lactation, and pregnancy + lactation), while downregulated TrkB protein expression (during pregnancy and pregnancy + lactation). SDG intervention attenuated these abnormalities by reducing the levels of inflammatory factors (low, medium, and high doses during pregnancy and lactation) and oxidative stress (medium and high doses during pregnancy and lactation), downregulating BDNF mRNA and protein expression, and upregulating TrkB protein expression (P < 0.05).

Conclusion  Maternal exposure to a TFA-enriched environment during pregnancy and lactation can induce varying degrees of structural and functional impairment in the brains of offspring and alter the expression levels of BDNF and TrkB proteins in the offspring brain. SDG intervention during TFA exposure exerts protective effects against brain injury in offspring mice, potentially by regulating BDNF and TrkB protein expression to appropriate levels, reactivating BDNF–TrkB downstream signaling pathways, and alleviating inflammatory and oxidative damage.