Postnatal choline supplementation rescues deficits in synaptic plasticity following prenatal ethanol exposure




Grafe, Erin L.
Wade, Mira M. M.
Hodson, Claire E.
Thomas, Jennifer D.
Christie, Brian R.

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Prenatal ethanol exposure (PNEE) is a leading cause of neurodevelopmental impairments, yet treatments for individuals with PNEE are limited. Importantly, postnatal supplementation with the essential nutrient choline can attenuate some adverse effects of PNEE on cognitive development; however, the mechanisms of action for choline supplementation remain unclear. This study used an animal model to determine if choline supplementation could restore hippocampal synaptic plasticity that is normally impaired by prenatal alcohol. Throughout gestation, pregnant Sprague Dawley rats were fed an ethanol liquid diet (35.5% ethanol-derived calories). Offspring were injected with choline chloride (100 mg/kg/day) from postnatal days (PD) 10–30, and then used for in vitro electrophysiology experiments as juveniles (PD 31–35). High-frequency conditioning stimuli were used to induce long-term potentiation (LTP) in the medial perforant path input to the dentate gyrus of the hippocampus. PNEE altered synaptic transmission in female offspring by increasing excitability, an effect that was mitigated with choline supplementation. In contrast, PNEE juvenile males had decreased LTP compared to controls, and this was rescued by choline supplementation. These data demonstrate sex-specific changes in plasticity following PNEE, and provide evidence that cholinerelated improvements in cognitive functioning may be due to its positive impact on hippocampal synaptic physiology.



prenatal ethanol exposure, fetal alcohol, hippocampus, synaptic plasticity, choline supplementation, dentate gyrus, sex differences, intervention


Grafe, E., Wade, M., Hodson, C., Thomas, J., & Christie, B. (2022). “Postnatal choline supplementation rescues deficits in synaptic plasticity following prenatal ethanol exposure.” Nutrients, 14(10), 2004.