Department of Anatomy, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea.
Department of Anatomy, School of Medicine and Jesaeng-Euise Clinical Anatomy Center, Wonkwang University, Iksan 54538, Republic of Korea.
Nutrients. 2023 Oct 10;15(20):4325. doi: 10.3390/nu15204325.
Obesity and heavy metals, such as lead (Pb), are detrimental to the adult brain because they impair cognitive function and structural plasticity. However, the effects of co-administration of Pb and a high-fat diet (HFD) on the developing cerebellum is not clearly elucidated. We investigated the effects of Pb exposure (0.3% lead acetate) on developing cerebellum in the pups of an HFD-fed obese rat model. One week before mating, we fed a chow diet (CD) or HFD to the rats for one week and additionally administered Pb to HFD-fed female SD rats. Thereafter, treatment with Pb and a HFD was continued during the gestational and lactational periods. On postnatal day 21, the pups were euthanized to sample the brain tissue and blood for further analysis. Blood Pb levels were significantly higher in HFD-fed rats than in CD-fed rats. Histologically, the prominent degeneration of Purkinje cells was induced by the co-administration of Pb and HFD. The calbindin-28Kd-, GAD67-, NMDAR1-, and PSD95-immunopositive Purkinje cells and inhibitory synapse-forming pinceau structures were significantly decreased following Pb and HFD co-administration. MBP-immunoreactive myelinated axonal fibers were also impaired by HFD but were significantly damaged by the co-administration of HFD and Pb. Oxidative stress-related Nrf2-HO1 signaling was activated by HFD feeding, and Pb exposure further aggravated oxidative stress, as demonstrated by the consumption of endogenous anti-oxidant in HFD-Pb rats. The pro-inflammatory response was also increased by the co-administration of HFD and Pb in the cerebellum of the rat offspring. The present results suggest that HFD and Pb treatment during the gestational and lactational periods are harmful to cerebellar development.
肥胖和重金属，如铅（Pb），对成人的大脑有害，因为它们会损害认知功能和结构可塑性。然而，Pb 与高脂肪饮食（HFD）共同作用对发育中的小脑的影响尚不清楚。我们研究了 Pb 暴露（0.3%醋酸铅）对 HFD 喂养肥胖大鼠模型后代发育中的小脑的影响。在交配前一周，我们用 CD 或 HFD 喂养大鼠一周，并向 HFD 喂养的雌性 SD 大鼠额外给予 Pb。此后，在妊娠期和哺乳期继续给予 Pb 和 HFD 治疗。在出生后第 21 天，处死幼鼠取样脑组织和血液进行进一步分析。HFD 喂养的大鼠血液中的 Pb 水平明显高于 CD 喂养的大鼠。组织学上，Pb 与 HFD 共同给药诱导浦肯野细胞明显退化。钙结合蛋白-28Kd、GAD67、NMDAR1 和 PSD95 免疫阳性的浦肯野细胞和抑制性突触形成的棘突结构在 Pb 和 HFD 共同给药后显著减少。髓鞘碱性蛋白免疫反应性有髓神经轴突纤维也受到 HFD 的损害，但 HFD 和 Pb 共同给药后损伤更为严重。Nrf2-HO1 信号通路与氧化应激相关，HFD 喂养激活了该通路，而 Pb 暴露进一步加重了氧化应激，这表现为 HFD-Pb 大鼠中内源性抗氧化剂的消耗。HFD 和 Pb 共同给药也增加了小脑的炎症反应。这些结果表明，妊娠期和哺乳期给予 HFD 和 Pb 对小脑发育有害。
