Alcohol, clinical & experimental research · 2026
Moderate Prenatal Alcohol Exposure Disrupts Brain Redox Homeostasis and the Activity of Tyrosine Phosphatase STEP in Adult Offspring.
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Bhattacharjee Anindita, Rajagopal Sathyanarayanan, Choi Seong Won, Weaver John, Liu Ke Jian, Poddar Ranjana, Caldwell Kevin K, Valenzuela C Fernando, Paul Surojit
Аннотация
BACKGROUND: Despite public health efforts, prenatal alcohol exposure (PAE) remains a significant concern. Its effects on offspring vary depending on the amount and frequency of drinking, and the risk of Fetal Alcohol Spectrum Disorders (FASDs) increases with heavy or binge drinking. In contrast, the long-term consequences of moderate PAE remain unclear. Although previous studies indicate that moderate PAE may have a limited impact on neurodevelopment, its ability to induce persistent cerebrovascular dysfunction may promote chronic low-level oxidative stress in the brain. Therefore, it is important to determine whether moderate PAE can trigger long-lasting impairments in brain function that persist into adulthood.
METHODS: The current study investigated the effect of moderate PAE on the brain's redox environment in adult (4-6 months) and middle-aged (12-14 months) offspring. Electron paramagnetic resonance (EPR) spectroscopy was used to noninvasively measure thiol levels in the brain. Biochemical assays measured levels of reduced and total glutathione, the primary thiol and major antioxidant in the brain. To determine the functional consequences of altered redox status, the study examined the dimerization status and enzymatic activity of the redox-sensitive and neuron-specific tyrosine phosphatase STEP (STriatal Enriched Phosphatase), a key regulator of synaptic signaling and neuroprotection.
RESULTS: The findings demonstrate that moderate PAE significantly reduces total thiol content and glutathione levels in adult male PAE offspring. This redox imbalance is accompanied by enhanced STEP dimerization and a concomitant reduction in STEP phosphatase activity. Notably, the redox imbalance and STEP dysfunction persisted into aging in male PAE offspring.
CONCLUSIONS: These findings demonstrate that moderate PAE leads to long-lasting alterations in the brain's redox homeostasis and compromises STEP function in male offspring. Such persistent dysfunction of the redox-sensitive neuroprotectant STEP may increase the vulnerability of male PAE offspring to neurological disorders later in life. Future studies would examine sex- and age-related interactions in PAE offspring.
METHODS: The current study investigated the effect of moderate PAE on the brain's redox environment in adult (4-6 months) and middle-aged (12-14 months) offspring. Electron paramagnetic resonance (EPR) spectroscopy was used to noninvasively measure thiol levels in the brain. Biochemical assays measured levels of reduced and total glutathione, the primary thiol and major antioxidant in the brain. To determine the functional consequences of altered redox status, the study examined the dimerization status and enzymatic activity of the redox-sensitive and neuron-specific tyrosine phosphatase STEP (STriatal Enriched Phosphatase), a key regulator of synaptic signaling and neuroprotection.
RESULTS: The findings demonstrate that moderate PAE significantly reduces total thiol content and glutathione levels in adult male PAE offspring. This redox imbalance is accompanied by enhanced STEP dimerization and a concomitant reduction in STEP phosphatase activity. Notably, the redox imbalance and STEP dysfunction persisted into aging in male PAE offspring.
CONCLUSIONS: These findings demonstrate that moderate PAE leads to long-lasting alterations in the brain's redox homeostasis and compromises STEP function in male offspring. Such persistent dysfunction of the redox-sensitive neuroprotectant STEP may increase the vulnerability of male PAE offspring to neurological disorders later in life. Future studies would examine sex- and age-related interactions in PAE offspring.