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

• Published in: Cells (Basel, Switzerland) Switzerland), 2022-12, Vol.12 (1), p.58
• Main Authors: Postnikova, Tatyana Y, Amakhin, Dmitry V, Trofimova, Alina M, Tumanova, Natalia L, Dubrovskaya, Nadezhda M, Kalinina, Daria S, Kovalenko, Anna A, Shcherbitskaia, Anastasiia D, Vasilev, Dmitry S, Zaitsev, Aleksey V
• Format: Article
• Language: English
• Subjects: Analysis; Animal cognition; Animals; Brain; Care and treatment; Cognition disorders; Cognitive ability; Dendritic spines; Diagnosis; Digitization; Electron microscopy; Female; Females; Fetuses; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Hippocampus; Hippocampus - metabolism; Homocysteine; Homocystinuria; Hyperhomocysteinemia; Hyperhomocysteinemia - complications; Hyperhomocysteinemia - metabolism; Immunofluorescence; Laboratories; Long-Term Potentiation; Memory; Memory Disorders - etiology; Memory Disorders - metabolism; N-Methyl-D-aspartic acid receptors; Neural networks; Neuronal Plasticity; NMDA receptor; Pregnancy; Pregnancy complications; Pregnancy, Complications of; Prenatal experience; Prevention; Rats; Risk factors; Software; Synaptic plasticity; Ultrastructure
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12010058

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.