Bisphenol A (BPA) is used to produce polycarbonate plastic and epoxy resins which are used in many consumer products. Most people encounter BPA in their daily routines. However, it has been heavily reported that BPA has a neurotoxic effect. The present study aimed to investigate the effect of lycopene on cognitive deficits induced by a high dose of BPA focusing on mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, oxidative stress, apoptosis, and memory retrieval in adult male rats. Therefore, 72 rats were divided into four groups: control group, BPA group (50 mg/kg body weight (bw)) 3 days a week for 42 days, lycopene group (10 mg/kg bw) daily for 42 days, and lycopene + BPA group. Concurrent treatment of lycopene with BPA improved the learning and cognition memory in Morris water maze and novel object recognition tests along with an increase in acetylcholine esterase activity as well as inhibition of oxidative stress by restoring reduced glutathione and suppressing malondialdehyde hippocampal level to their normal levels. Mechanistically, lycopene upregulated the protein expression of tyrosine receptor kinase B, which resulted in an upsurge in its downstream cascades MAPK/ERK1/2/cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway in the hippocampus of BPA-intoxicated rats. Furthermore, concurrent treatment of lycopene with BPA prevented apoptosis by marked decrease in Bcl-2 associated X protein (Bax) gene expression and caspase 3 activity while restoring B-cell leukemia/lymphoma-2 (Bcl-2) gene expression. In conclusion, the present study provided evidence that lycopene exerted a neuroprotective effect against BPA intoxication in hippocampi of rats via its antioxidant properties, activation of MAPK/ERK pathway, and inhibiting a neuronal apoptosis which reflected on improving the learning and cognition memory.

双酚A（BPA）用于生产用于许多消费品的聚碳酸酯塑料和环氧树脂。大多数人在日常生活中都会遇到BPA。然而，大量报道BPA具有神经毒性作用。本研究旨在研究番茄红素对高剂量BPA引起的认知功能障碍的影响，重点在于有丝分裂原激活的蛋白激酶（MAPK）/细胞外信号调节激酶（ERK）途径，氧化应激，细胞凋亡和记忆恢复成年雄性大鼠。因此，将72只大鼠分为四组：对照组，BPA组（50 mg / kg体重（bw）），每周3天，共42天；番茄红素组（10 mg / kg bw），每天，共42天；番茄红素。 + BPA组。番茄红素与BPA的同时处理改善了莫里斯水迷宫中的学习和认知记忆以及新颖的物体识别测试，并通过恢复还原型谷胱甘肽和抑制丙二醛海马水平至正常水平来提高乙酰胆碱酯酶活性以及抑制氧化应激。从机制上讲，番茄红素上调酪氨酸受体激酶B的蛋白表达，从而导致其下游级联反应中的MAPK / ERK1 / 2 / cAMP反应元件结合蛋白（CREB）/脑源性神经营养因子（BDNF）信号通路增高。 BPA致醉大鼠的海马区。此外，番茄红素与BPA的同时治疗通过显着降低Bcl-2相关X蛋白（Bax）基因表达和caspase 3活性来预防细胞凋亡，同时恢复B细胞白血病/淋巴瘤2（Bcl-2）基因表达。总之，本研究提供了证据表明番茄红素通过其抗氧化特性，MAPK / ERK途径的激活和抑制神经元凋亡对大鼠海马中的BPA中毒发挥了神经保护作用，这反映了其学习和认知记忆的改善。