Maternal Hyperhomocysteinemia Produces Memory Deficits Associated with Impairment of Long-Term Synaptic Plasticity in Young Rats

Abstract

Maternal hyperhomocysteinemia (HCY) is a common pregnancy complication caused by high levels of the homocysteine in maternal and fetal blood, which leads to the alterations of the cognitive functions, including learning and memory. In the present study, we investigated the mechanisms of these alterations in a rat model of maternal HCY. The behavioral tests confirmed the memory impairments in young and adult rats following the prenatal HCY exposure. Field potential recordings in hippocampal slices demonstrated that the long-term potentiation (LTP) was significantly reduced in HCY rats. The whole-cell patch-clamp recordings in hippocampal slices demonstrated that the magnitude of NMDA receptor-mediated currents did not change while their desensitization decreased in HCY rats. No significant alterations of glutamate receptor subunit expression except GluN1 were detected in the hippocampus of HCY rats using the quantitative real-time PCR and Western blot methods. The immunofluorescence microscopy revealed that the number of synaptopodin-positive spines is reduced, while the analysis of the ultrastructure of hippocampus using the electron microscopy revealed the indications of delayed hippocampal maturation in young HCY rats. Thus, the obtained results suggest that maternal HCY disturbs the maturation of hippocampus during the first month of life, which disrupts LTP formation and causes memory impairments.

The Role of Methionine-Rich Diet in Unhealthy Cerebrovascular and Brain Aging: Mechanisms and Implications for Cognitive Impairment

“…Synaptic plasticity, the ability of synapses to strengthen or weaken over time in response to changes in their activity, is fundamental to learning and memory processes. High methionine intake and hyperhomocysteinemia have been shown to impact synaptic plasticity by disrupting key molecular signaling pathways involved in synaptic function [223,[350][351][352][353][354]. Preclinical studies have demonstrated that a methionine-rich diet can impair long-term potentiation (LTP), a cellular mechanism underlying synaptic plasticity, leading to deficits in learning and memory [351,354,355].…”

“…High methionine intake and hyperhomocysteinemia have been shown to impact synaptic plasticity by disrupting key molecular signaling pathways involved in synaptic function [223,[350][351][352][353][354]. Preclinical studies have demonstrated that a methionine-rich diet can impair long-term potentiation (LTP), a cellular mechanism underlying synaptic plasticity, leading to deficits in learning and memory [351,354,355]. Elevated homocysteine levels, stemming from high methionine intake, have been linked to reduced levels of brain-derived neurotrophic factor (BDNF) [356], a molecule essential for synaptic plasticity.…”