Postnatal Choline Supplementation Rescues Deficits in Synaptic Plasticity Following Prenatal Ethanol Exposure

Abstract

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 choline-related improvements in cognitive functioning may be due to its positive impact on hippocampal synaptic physiology.

Choline Supplementation Modifies the Effects of Developmental Alcohol Exposure on Immune Responses in Adult Rats

“…Preclinical models have demonstrated that choline supplementation can attenuate the effects of developmental alcohol exposure, specifically alcohol-induced behavioral and cognitive alterations [ 29 , 30 , 31 , 32 , 33 , 34 ]. Moreover, choline can improve hippocampal-dependent learning and memory [ 29 , 30 , 31 , 34 ] and can enhance hippocampal plasticity [ 35 ], even when administered after developmental ethanol exposure. Recent clinical studies in FASD support preclinical findings, with cognitive improvements reported in children who received choline supplementation either prenatally [ 36 , 37 ] or postnatally [ 38 , 39 ].…”

Choline supplementation in early life improves and low levels of choline can impair outcomes in a mouse model of Alzheimer’s disease

“…Although few studies have examined the effects of MCS on hyperexcitability, our results showing the benefits of high choline are consistent with reports that a methyl-enriched diet (including choline but also betaine, folic acid, vitamin B12, L-methionine and zinc) reduced spike wave discharges (Sarkisova et al 2023) and audiogenic seizure severity (Poletaeva et al 2014) in the offspring. Perinatal ethanol treatment that increased excitability was mitigated by choline chloride injection from postnatal day 10-30 (Grafe et al 2022).…”

“…Perinatal ethanol treatment that increased excitability was mitigated by choline chloride injection from postnatal day 10-30 (Grafe et al, 2022).…”

Neuroimmune Interactions in Fetal Alcohol Spectrum Disorders: Potential Therapeutic Targets and Intervention Strategies

“…In an animal study, Sprague–Dawley rat pups received ethanol (5.25 g/kg/day) from PD 4–9 and choline chloride (100 mg/kg/day) from PD 10–30—the hippocampus collected from these rats at PD 35 or PD 60 showed choline mitigated the long tasting effect of ethanol on inflammatory tone via modulating the ratio of pro-to-anti-inflammatory cytokines [ 102 , 103 ]. In vitro electrophysiology experiments at PD 30–35 in choline-supplemented juvenile males and females from PD 10–30 showed a positive effect on hippocampal synaptic physiology that may be attributed to choline-related improvement in cognitive function [ 104 ]. Prenatal supplementation of choline (642 mg/L) in mice was found to prevent gross developmental abnormalities associated with prenatal alcohol (25%) exposure [ 105 ].…”