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Evaluation of TRPM2 Channel‐Mediated Autophagic Signaling Pathway in Hippocampus and Cortex Tissues of Rat Offspring Following Prenatal Exposure to Elevated Alcohol Levels
Environmental Toxicology ( IF 4.4 ) Pub Date : 2024-10-10 , DOI: 10.1002/tox.24427 Abdülhadi Cihangir Uğuz, Aslı Okan, Züleyha Doğanyiğit, Seher Yilmaz, Şükrü Ateş, Evrim Suna Arikan Söylemez, Sebahattin Karabulut, Alper Serhat Kumru, Javier Espino
Environmental Toxicology ( IF 4.4 ) Pub Date : 2024-10-10 , DOI: 10.1002/tox.24427 Abdülhadi Cihangir Uğuz, Aslı Okan, Züleyha Doğanyiğit, Seher Yilmaz, Şükrü Ateş, Evrim Suna Arikan Söylemez, Sebahattin Karabulut, Alper Serhat Kumru, Javier Espino
Fetal alcohol syndrome (FAS) can occur because of high amount of alcohol intake during pregnancy and is characterized by both physical and neurological problems. Children diagnosed with FAS have difficulties in learning, memory, and coordination. Hippocampus has a major role in memory and learning. We aimed to determine whether alcohol exposure during pregnancy had any effect on offspring by evaluating learning ability as well as oxidative stress and autophagy in the hippocampus and cortex tissues of litters. Attention was also paid to sex differences. To do so, TRPM2, Beclin1, p62, LC3B, IBA1, parvalbumin, GAD65, and mGluR5 expression levels were evaluated by immunohistochemistry. Lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels, as well as total oxidant (TOS) and total antioxidant (TAS) status were determined by ELISA. Learning experiments were evaluated by the Morris water maze (MWM) test. Our findings demonstrated that IBA1, LC3B, GAD65, and mGluR5 expression levels were higher in female rats of the chronic alcohol exposure (CAE) model. Our IHC results revealed that TRPM2 expression levels were significantly increased in both males and females in the CAE group. Likewise, TAS was lower, and TOS was higher in CAE animals. Moreover, MWM outcomes supported a learning deficiency in CAE litters compared to controls and indicated that female offspring outperformed males in learning experiments. Therefore, our results revealed the detrimental effects of alcohol exposure during pregnancy on autophagy signaling in the hippocampus and cortex tissue of litters, which could affect the learning ability of animals.
中文翻译:
产前暴露于高酒精水平后大鼠后代海马和皮层组织中 TRPM2 通道介导的自噬信号通路的评价
胎儿酒精综合征 (FAS) 可能是由于怀孕期间大量饮酒而发生的,其特征是身体和神经系统问题。被诊断患有 FAS 的儿童在学习、记忆和协调方面存在困难。海马体在记忆和学习中起着重要作用。我们旨在通过评估幼崽海马体和皮层组织中的学习能力以及氧化应激和自噬来确定怀孕期间酒精暴露是否对后代有任何影响。还关注了性别差异。为此,通过免疫组织化学评估 TRPM2 、 Beclin1 、 p62 、 LC3B 、 IBA1 、 parvalbumin 、 GAD65 和 mGluR5 表达水平。ELISA 测定乳酸脱氢酶 (LDH) 和丙二醛 (MDA) 水平,以及总氧化剂 (TOS) 和总抗氧化 (TAS) 状态。通过莫里斯水迷宫 (MWM) 测试评估学习实验。我们的研究结果表明,慢性酒精暴露 (CAE) 模型的雌性大鼠 IBA1 、 LC3B 、 GAD65 和 mGluR5 表达水平较高。我们的 IHC 结果显示,CAE 组男性和女性的 TRPM2 表达水平均显著升高。同样,CAE 动物的 TAS 较低,而 TOS 较高。此外,与对照组相比,MWM 结果支持 CAE 窝的学习缺陷,并表明女性后代在学习实验中的表现优于男性。因此,我们的结果揭示了怀孕期间酒精暴露对窝体海马体和皮层组织中自噬信号传导的不利影响,这可能会影响动物的学习能力。
更新日期:2024-10-10
中文翻译:
产前暴露于高酒精水平后大鼠后代海马和皮层组织中 TRPM2 通道介导的自噬信号通路的评价
胎儿酒精综合征 (FAS) 可能是由于怀孕期间大量饮酒而发生的,其特征是身体和神经系统问题。被诊断患有 FAS 的儿童在学习、记忆和协调方面存在困难。海马体在记忆和学习中起着重要作用。我们旨在通过评估幼崽海马体和皮层组织中的学习能力以及氧化应激和自噬来确定怀孕期间酒精暴露是否对后代有任何影响。还关注了性别差异。为此,通过免疫组织化学评估 TRPM2 、 Beclin1 、 p62 、 LC3B 、 IBA1 、 parvalbumin 、 GAD65 和 mGluR5 表达水平。ELISA 测定乳酸脱氢酶 (LDH) 和丙二醛 (MDA) 水平,以及总氧化剂 (TOS) 和总抗氧化 (TAS) 状态。通过莫里斯水迷宫 (MWM) 测试评估学习实验。我们的研究结果表明,慢性酒精暴露 (CAE) 模型的雌性大鼠 IBA1 、 LC3B 、 GAD65 和 mGluR5 表达水平较高。我们的 IHC 结果显示,CAE 组男性和女性的 TRPM2 表达水平均显著升高。同样,CAE 动物的 TAS 较低,而 TOS 较高。此外,与对照组相比,MWM 结果支持 CAE 窝的学习缺陷,并表明女性后代在学习实验中的表现优于男性。因此,我们的结果揭示了怀孕期间酒精暴露对窝体海马体和皮层组织中自噬信号传导的不利影响,这可能会影响动物的学习能力。