Retardation of neurobehavioral development and reelin down-regulation regulated by further DNA methylation in the hippocampus of the rat pups are associated with maternal deprivation.
It is known that early life stress has profound effects in early developing hippocampus. Reelin is a large protein that regulates neuronal migration during embryonic development. The expression of reelin persists in brain, but its function is little known. The aim of the present study was to investigate the effects of maternal deprivation (MD) on early neurobehavioral development of rats, and the role of reelin and the potential mechanism underlying regulation of its expression in hippocampus. Rat pups were removed from mothers during the postnatal day (PND) 2-15 for 3h a day. Reflex developments including grasping, gait, righting, cliff avoidance, auditory startle, hot-plate test and negative geotaxis, were tested during the first 3 weeks. The level of reelin mRNA and reelin gene methylation in the hippocampal formation were determined using real-time PCR analysis. As expected, some differences appeared in the measure of neurobehavior and expression of reelin in rat pups. Several significant deficiencies were observed in bodyweight, auditory startle and grasping reflex while a great enhancement in hot-plate test in rat pups suffering from MD. On PND 22, the expression of reelin mRNA reduced in the hippocampus followed by MD. Meanwhile, the changes of DNA methylation showed an opposite trend compared with the reelin expression. The results suggest that MD in early life has harmful effects on neurobehavioral development, and causes the down-regulation of reelin mRNA by further DNA methylation in postnatal hippocampus.
Department of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Lina
L
Qin
Wenqiang
W
Tu
Xiumin
X
Sun
Jianlong
J
Zhang
Yuchuan
Y
Chen
Hu
H
Zhao
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001835:Body Weight; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D019175:DNA Methylation; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism*; D008297:Male; D008426:Maternal Deprivation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology*
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717129:Reln protein, rat; D012697:Serine Endopeptidases