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Evaluation of TRPM2 Channel-Mediated Autophagic Signaling Pathway in Hippocampus and Cortex Tissues of Rat Offspring
Abdülhadi Cihangir Uğuz1, Aslı Okan2, Züleyha Doğanyiğit2
1Department of Biophysics, School of Medicine, Karamanoğlu Mehmetbey University, Karaman, Türkiye.
Insights
Prenatal alcohol exposure impairs offspring learning and memory by disrupting hippocampal and cortical autophagy signaling. This study highlights sex differences in these detrimental effects.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Fetal alcohol syndrome (FAS) results from prenatal alcohol exposure, causing physical and neurological deficits, including impaired learning and memory.
- The hippocampus is crucial for memory and learning, and its function may be compromised by alcohol-induced oxidative stress and altered autophagy.
Purpose of the Study:
- To investigate the effects of chronic alcohol exposure during pregnancy on offspring learning, memory, oxidative stress, and autophagy in hippocampus and cortex.
- To examine potential sex differences in the neurobiological consequences of prenatal alcohol exposure.
Main Methods:
- Evaluated learning ability using the Morris water maze (MWM) test.
- Assessed expression levels of TRPM2, Beclin1, p62, LC3B, IBA1, parvalbumin, GAD65, and mGluR5 via immunohistochemistry.
- Measured lactate dehydrogenase (LDH), malondialdehyde (MDA), total oxidant status (TOS), and total antioxidant status (TAS) using ELISA.
Main Results:
- Chronic alcohol exposure (CAE) led to learning deficiencies in offspring, with females showing better performance than males.
- CAE altered autophagy signaling, indicated by increased IBA1, LC3B, GAD65, and mGluR5 in females, and increased TRPM2 in both sexes.
- Prenatal alcohol exposure resulted in increased oxidative stress (higher TOS, lower TAS) in the offspring.
Conclusions:
- Prenatal alcohol exposure detrimentally impacts autophagy signaling and learning ability in offspring hippocampus and cortex.
- Oxidative stress and altered autophagy are key mechanisms underlying neurodevelopmental deficits caused by FAS.
- Sex-specific differences exist in the response to prenatal alcohol exposure, influencing learning outcomes and molecular changes.
Abstract:
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.
